Harold L. Moses, M.D.

Research Professor

Faculty Appointments
Research Professor of Pharmacology Professor of Cancer Biology, EmeritusProfessor of MedicineProfessor of Pathology, Microbiology and Immunology
M.D., Medicine, Vanderbilt University, Nashville, TennesseeB.A., Chemistry, Berea College , Berea, Kentucky
Office Address
691 PRB
TN 6838
Research Description
Accumulating data indicate that the stroma can play a critical role in cancer initiation and progression. TGF-beta signaling in both epithelial and stromal cells appears to be a key regulator of the stromal microenvironment. There is now compelling evidence from transgenic mouse studies and analyses of mutations in human carcinomas indicating that the TGF-beta signal transduction pathway is tumor suppressive. Studies of human tumors have demonstrated inactivating mutations in human tumors of genes encoding proteins involved in TGF-beta signal transduction, including DPC4/Smad4, Smad2, and the type I and type II TGF-beta receptor (TßRI and TßRII, respectively). However, there is some evidence that TGF-beta signaling can promote tumor progression in the later stages. In order to examine the roles of TGF-beta signaling in cancer more closely, we have generated mice with loxP sites flanking exon 2 of the type II receptor gene, Tgfbr2, and crossed them with mice expressing Cre driven by different epithelial specific promoters. Loss of TGF-beta signaling in six different epithelial cells gave a minimal phenotype. However, when challenged with oncogene expression or tumor suppressor gene impairment, there was rapid development of invasive and metastatic carcinomas supporting the hypothesis that epithelial cell autonomous TGF-beta signaling is tumor suppressive in both early and late stages of carcinogenesis. One mechanism appears to be enhanced expression of chemokines by Tgfbr2 null carcinoma cells with resultant recruitment of bone marrow derived cells that express abundant TGF-beta and MMPs in the tumor microenvironment and promote invasion and metastasis.

In contrast to the epithelial cell knockouts that gave a minimal phenotype, knockout of Tgfbr2 in stromal fibroblasts gave a striking epithelial phenotype in the mammary gland, prostate and forestomach, including epithelial pre-neoplasia and invasive carcinomas. One mechanism identified was paracrine stimulation of carcinoma cells by HGF, MSP and TGF-alpha. Another mechanism appeared to be over expression of chemokines by the knockout fibroblasts with recruitment of bone marrow derived cells. Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues. The data indicate that TGF-beta signaling is a major regulator of chemokine secretion and resultant bone marrow cell infiltration and that targeting pathways that inhibit bone marrow cell differentiation or chemokine receptors may be useful in both therapy and prevention of cancer.

Research Keywords
Regulation of cell proliferation by growth factors, oncogenes, growth inhibitors and tumor suppressor genes.
Bierie B, Chung CH, Parker JS, Stover DG, Cheng N, Chytil A, Aakre M, Shyr Y, Moses HL. Abrogation of TGF-beta signaling enhances chemokine production and correlates with prognosis in human breast cancer. J. Clin. Invest [print-electronic]. 2009 Jun; 119(6): 1571-82. PMID: 19451693, PMCID: PMC2689133, PII: 37480, DOI: 10.1172/JCI37480, ISSN: 1558-8238.

Abel TW, Clark C, Bierie B, Chytil A, Aakre M, Gorska A, Moses HL. GFAP-Cre-mediated activation of oncogenic K-ras results in expansion of the subventricular zone and infiltrating glioma. Mol. Cancer Res [print-electronic]. 2009 May; 7(5): 645-53. PMID: 19435821, PMCID: PMC3406747, PII: 1541-7786.MCR-08-0477, DOI: 10.1158/1541-7786.MCR-08-0477, ISSN: 1541-7786.

Bierie B, Gorska AE, Stover DG, Moses HL. TGF-beta promotes cell death and suppresses lactation during the second stage of mammary involution. J. Cell. Physiol. 2009 Apr; 219(1): 57-68. PMID: 19086032, PMCID: PMC3038423, DOI: 10.1002/jcp.21646, ISSN: 1097-4652.

Erdogan M, Pozzi A, Bhowmick N, Moses HL, Zent R. Transforming growth factor-beta (TGF-beta) and TGF-beta-associated kinase 1 are required for R-Ras-mediated transformation of mammary epithelial cells. Cancer Res. 2008 Aug 8/1/2008; 68(15): 6224-31. PMID: 18676846, PII: 68/15/6224, DOI: 10.1158/0008-5472.CAN-08-0513, ISSN: 1538-7445.

Bierie B, Stover DG, Abel TW, Chytil A, Gorska AE, Aakre M, Forrester E, Yang L, Wagner KU, Moses HL. Transforming growth factor-beta regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment. Cancer Res. 2008 Mar 3/15/2008; 68(6): 1809-19. PMID: 18339861, PII: 68/6/1809, DOI: 10.1158/0008-5472.CAN-07-5597, ISSN: 1538-7445.

Yang L, Huang J, Ren X, Gorska AE, Chytil A, Aakre M, Carbone DP, Matrisian LM, Richmond A, Lin PC, Moses HL. Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell. 2008 Jan; 13(1): 23-35. PMID: 18167337, PMCID: PMC2245859, PII: S1535-6108(07)00373-X, DOI: 10.1016/j.ccr.2007.12.004, ISSN: 1535-6108.

Erdogan M, Pozzi A, Bhowmick N, Moses HL, Zent R. Signaling pathways regulating TC21-induced tumorigenesis. J. Biol. Chem [print-electronic]. 2007 Sep 9/21/2007; 282(38): 27713-20. PMID: 17656362, PII: M703037200, DOI: 10.1074/jbc.M703037200, ISSN: 0021-9258.

Stover DG, Bierie B, Moses HL. A delicate balance: TGF-beta and the tumor microenvironment. J. Cell. Biochem. 2007 Jul 7/1/2007; 101(4): 851-61. PMID: 17486574, DOI: 10.1002/jcb.21149, ISSN: 0730-2312.

Spagnoli A, O'Rear L, Chandler RL, Granero-Molto F, Mortlock DP, Gorska AE, Weis JA, Longobardi L, Chytil A, Shimer K, Moses HL. TGF-beta signaling is essential for joint morphogenesis. J. Cell Biol. 2007 Jun 6/18/2007; 177(6): 1105-17. PMID: 17576802, PMCID: PMC2064369, PII: jcb.200611031, DOI: 10.1083/jcb.200611031, ISSN: 0021-9525.

Cheng N, Chytil A, Shyr Y, Joly A, Moses HL. Enhanced hepatocyte growth factor signaling by type II transforming growth factor-beta receptor knockout fibroblasts promotes mammary tumorigenesis. Cancer Res [print-electronic]. 2007 May 5/15/2007; 67(10): 4869-77. PMID: 17495323, PII: 0008-5472.CAN-06-3381, DOI: 10.1158/0008-5472.CAN-06-3381, ISSN: 0008-5472.

Biswas S, Guix M, Rinehart C, Dugger TC, Chytil A, Moses HL, Freeman ML, Arteaga CL. Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J. Clin. Invest [print-electronic]. 2007 May; 117(5): 1305-13. PMID: 17415413, PMCID: PMC1838926, DOI: 10.1172/JCI30740, ISSN: 0021-9738.

Brown KA, Pietenpol JA, Moses HL. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J. Cell. Biochem. 2007 May 5/1/2007; 101(1): 9-33. PMID: 17340614, DOI: 10.1002/jcb.21255, ISSN: 0730-2312.

Bonine-Summers AR, Aakre ME, Brown KA, Arteaga CL, Pietenpol JA, Moses HL, Cheng N. Epidermal growth factor receptor plays a significant role in hepatocyte growth factor mediated biological responses in mammary epithelial cells. Cancer Biol. Ther. 2007 Apr; 6(4): 561-70. PMID: 17495520, PMCID: PMC3395216, PII: 3851, ISSN: 1538-4047.

Hoshino A, Yee CJ, Campbell M, Woltjer RL, Townsend RL, van der Meer R, Shyr Y, Holt JT, Moses HL, Jensen RA. Effects of BRCA1 transgene expression on murine mammary gland development and mutagen-induced mammary neoplasia. Int. J. Biol. Sci. 2007; 3(5): 281-91. PMID: 17505536, PMCID: PMC1865089, ISSN: 1449-2288.

Ijichi H, Chytil A, Gorska AE, Aakre ME, Fujitani Y, Fujitani S, Wright CV, Moses HL. Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-beta signaling in cooperation with active Kras expression. Genes Dev. 2006 Nov 11/15/2006; 20(22): 3147-60. PMID: 17114585, PMCID: PMC1635149, PII: 20/22/3147, DOI: 10.1101/gad.1475506, ISSN: 0890-9369.

Jiao K, Langworthy M, Batts L, Brown CB, Moses HL, Baldwin HS. Tgfbeta signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development. Development [print-electronic]. 2006 Nov; 133(22): 4585-93. PMID: 17050629, PII: dev.02597, DOI: 10.1242/dev.02597, ISSN: 0950-1991.

Muñoz NM, Upton M, Rojas A, Washington MK, Lin L, Chytil A, Sozmen EG, Madison BB, Pozzi A, Moon RT, Moses HL, Grady WM. Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation. Cancer Res. 2006 Oct 10/15/2006; 66(20): 9837-44. PMID: 17047044, PII: 66/20/9837, DOI: 10.1158/0008-5472.CAN-06-0890, ISSN: 0008-5472.

Bierie B, Moses HL. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat. Rev. Cancer. 2006 Jul; 6(7): 506-20. PMID: 16794634, PII: nrc1926, DOI: 10.1038/nrc1926, ISSN: 1474-175X.

Halder SK, Anumanthan G, Maddula R, Mann J, Chytil A, Gonzalez AL, Washington MK, Moses HL, Beauchamp RD, Datta PK. Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis. Cancer Res. 2006 Jun 6/15/2006; 66(12): 6156-66. PMID: 16778189, PII: 66/12/6156, DOI: 10.1158/0008-5472.CAN-05-3261, ISSN: 0008-5472.

Longobardi L, O'Rear L, Aakula S, Johnstone B, Shimer K, Chytil A, Horton WA, Moses HL, Spagnoli A. Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J. Bone Miner. Res [print-electronic]. 2006 Apr; 21(4): 626-36. PMID: 16598383, DOI: 10.1359/jbmr.051213, ISSN: 0884-0431.

Bierie B, Moses HL. TGF-beta and cancer. Cytokine Growth Factor Rev [print-electronic]. 2006 Feb; 17(1-2): 29-40. PMID: 16289860, PII: S1359-6101(05)00110-3, DOI: 10.1016/j.cytogfr.2005.09.006, ISSN: 1359-6101.

Bierie B, Moses HL. Under pressure: stromal fibroblasts change their ways. Cell. 2005 Dec 12/16/2005; 123(6): 985-7. PMID: 16360028, PII: S0092-8674(05)01317-6, DOI: 10.1016/j.cell.2005.11.029, ISSN: 0092-8674.

Xie L, Xu BJ, Gorska AE, Shyr Y, Schwartz SA, Cheng N, Levy S, Bierie B, Caprioli RM, Moses HL. Genomic and proteomic analysis of mammary tumors arising in transgenic mice. J. Proteome Res. 2005 Nov; 4(6): 2088-98. PMID: 16335954, DOI: 10.1021/pr050214l, ISSN: 1535-3893.

Cheng N, Bhowmick NA, Chytil A, Gorksa AE, Brown KA, Muraoka R, Arteaga CL, Neilson EG, Hayward SW, Moses HL. Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated signaling networks. Oncogene. 2005 Jul 7/28/2005; 24(32): 5053-68. PMID: 15856015, PMCID: PMC3074577, PII: 1208685, DOI: 10.1038/sj.onc.1208685, ISSN: 0950-9232.

O'Rear L, Longobardi L, Torello M, Law BK, Moses HL, Chiarelli F, Spagnoli A. Signaling cross-talk between IGF-binding protein-3 and transforming growth factor-(beta) in mesenchymal chondroprogenitor cell growth. J. Mol. Endocrinol. 2005 Jun; 34(3): 723-37. PMID: 15956343, PII: 34/3/723, DOI: 10.1677/jme.1.01746, ISSN: 0952-5041.

Means AL, Chytil A, Moses HL, Coffey RJ, Wright CV, Taketo MM, Grady WM. Keratin 19 gene drives Cre recombinase expression throughout the early postimplantation mouse embryo. Genesis. 2005 May; 42(1): 23-7. PMID: 15828001, DOI: 10.1002/gene.20119, ISSN: 1526-954X.

Romero-Gallo J, Sozmen EG, Chytil A, Russell WE, Whitehead R, Parks WT, Holdren MS, Her MF, Gautam S, Magnuson M, Moses HL, Grady WM. Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy. Oncogene. 2005 Apr 4/21/2005; 24(18): 3028-41. PMID: 15735717, PII: 1208475, DOI: 10.1038/sj.onc.1208475, ISSN: 0950-9232.

Desgrosellier JS, Mundell NA, McDonnell MA, Moses HL, Barnett JV. Activin receptor-like kinase 2 and Smad6 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev. Biol. 2005 Apr 4/1/2005; 280(1): 201-10. PMID: 15766759, PII: S0012-1606(05)00048-5, DOI: 10.1016/j.ydbio.2004.12.037, ISSN: 0012-1606.

Forrester E, Chytil A, Bierie B, Aakre M, Gorska AE, Sharif-Afshar AR, Muller WJ, Moses HL. Effect of conditional knockout of the type II TGF-beta receptor gene in mammary epithelia on mammary gland development and polyomavirus middle T antigen induced tumor formation and metastasis. Cancer Res. 2005 Mar 3/15/2005; 65(6): 2296-302. PMID: 15781643, PII: 65/6/2296, DOI: 10.1158/0008-5472.CAN-04-3272, ISSN: 0008-5472.

Bhowmick NA, Moses HL. Tumor-stroma interactions. Curr. Opin. Genet. Dev. 2005 Feb; 15(1): 97-101. PMID: 15661539, PMCID: PMC2819733, PII: S0959-437X(04)00189-3, DOI: 10.1016/j.gde.2004.12.003, ISSN: 0959-437X.

Bhowmick NA, Neilson EG, Moses HL. Stromal fibroblasts in cancer initiation and progression. Nature. 2004 Nov 11/18/2004; 432(7015): 332-7. PMID: 15549095, PMCID: PMC3050735, PII: nature03096, DOI: 10.1038/nature03096, ISSN: 1476-4687.

Xie L, Law BK, Chytil AM, Brown KA, Aakre ME, Moses HL. Activation of the Erk pathway is required for TGF-beta1-induced EMT in vitro. Neoplasia. 2004 Sep; 6(5): 603-10. PMID: 15548370, PMCID: PMC1531665, DOI: 10.1593/neo.04241, ISSN: 1522-8002.

Biswas S, Chytil A, Washington K, Romero-Gallo J, Gorska AE, Wirth PS, Gautam S, Moses HL, Grady WM. Transforming growth factor beta receptor type II inactivation promotes the establishment and progression of colon cancer. Cancer Res. 2004 Jul 7/15/2004; 64(14): 4687-92. PMID: 15256431, PII: 64/14/4687, DOI: 10.1158/0008-5472.CAN-03-3255, ISSN: 0008-5472.

Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science. 2004 Feb 2/6/2004; 303(5659): 848-51. PMID: 14764882, PII: 303/5659/848, DOI: 10.1126/science.1090922, ISSN: 1095-9203.

Brown KA, Aakre ME, Gorska AE, Price JO, Eltom SE, Pietenpol JA, Moses HL. Induction by transforming growth factor-beta1 of epithelial to mesenchymal transition is a rare event in vitro. Breast Cancer Res [print-electronic]. 2004; 6(3): R215-31. PMID: 15084245, PMCID: PMC400675, PII: bcr778, DOI: 10.1186/bcr778, ISSN: 1465-542X.

Bhowmick NA, Ghiassi M, Aakre M, Brown K, Singh V, Moses HL. TGF-beta-induced RhoA and p160ROCK activation is involved in the inhibition of Cdc25A with resultant cell-cycle arrest. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2003 Dec 12/23/2003; 100(26): 15548-53. PMID: 14657354, PMCID: PMC307605, PII: 2536483100, DOI: 10.1073/pnas.2536483100, ISSN: 0027-8424.

Muraoka RS, Koh Y, Roebuck LR, Sanders ME, Brantley-Sieders D, Gorska AE, Moses HL, Arteaga CL. Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor beta1. Mol. Cell. Biol. 2003 Dec; 23(23): 8691-703. PMID: 14612410, PMCID: PMC262670, ISSN: 0270-7306.

Gorska AE, Jensen RA, Shyr Y, Aakre ME, Bhowmick NA, Moses HL. Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-beta receptor exhibit impaired mammary development and enhanced mammary tumor formation. Am. J. Pathol. 2003 Oct; 163(4): 1539-49. PMID: 14507660, PMCID: PMC1868288, PII: S0002-9440(10)63510-9, ISSN: 0002-9440.

Tu WH, Thomas TZ, Masumori N, Bhowmick NA, Gorska AE, Shyr Y, Kasper S, Case T, Roberts RL, Shappell SB, Moses HL, Matusik RJ. The loss of TGF-beta signaling promotes prostate cancer metastasis. Neoplasia. 2003 May; 5(3): 267-77. PMID: 12869309, PMCID: PMC1502411, DOI: NO_DOI, ISSN: 1522-8002.

Xie L, Law BK, Aakre ME, Edgerton M, Shyr Y, Bhowmick NA, Moses HL. Transforming growth factor beta-regulated gene expression in a mouse mammary gland epithelial cell line. Breast Cancer Res [print-electronic]. 2003; 5(6): R187-98. PMID: 14580254, PMCID: PMC314403, PII: bcr640, DOI: 10.1186/bcr640, ISSN: 1465-542X.

Law BK, Chytil A, Dumont N, Hamilton EG, Waltner-Law ME, Aakre ME, Covington C, Moses HL. Rapamycin potentiates transforming growth factor beta-induced growth arrest in nontransformed, oncogene-transformed, and human cancer cells. Mol. Cell. Biol. 2002 Dec; 22(23): 8184-98. PMID: 12417722, PMCID: PMC134072, ISSN: 0270-7306.

Chytil A, Magnuson MA, Wright CV, Moses HL. Conditional inactivation of the TGF-beta type II receptor using Cre:Lox. Genesis. 2002 Feb; 32(2): 73-5. PMID: 11857781, PII: 10.1002/gene.10046, ISSN: 1526-954X.

Bhowmick NA, Zent R, Ghiassi M, McDonnell M, Moses HL. Integrin beta 1 signaling is necessary for transforming growth factor-beta activation of p38MAPK and epithelial plasticity. J. Biol. Chem [print-electronic]. 2001 Dec 12/14/2001; 276(50): 46707-13. PMID: 11590169, PII: M106176200, DOI: 10.1074/jbc.M106176200, ISSN: 0021-9258.

Bragg AD, Moses HL, Serra R. Signaling to the epithelium is not sufficient to mediate all of the effects of transforming growth factor beta and bone morphogenetic protein 4 on murine embryonic lung development. Mech. Dev. 2001 Nov; 109(1): 13-26. PMID: 11677049, PII: S0925-4773(01)00508-1, ISSN: 0925-4773.

McDonnell MA, Law BK, Serra R, Moses HL. Antagonistic effects of TGFbeta1 and BMP-6 on skin keratinocyte differentiation. Exp. Cell Res. 2001 Feb 2/15/2001; 263(2): 265-73. PMID: 11161725, PII: S0014-4827(00)95117-6, DOI: 10.1006/excr.2000.5117, ISSN: 0014-4827.

Bhowmick NA, Ghiassi M, Bakin A, Aakre M, Lundquist CA, Engel ME, Arteaga CL, Moses HL. Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol. Biol. Cell. 2001 Jan; 12(1): 27-36. PMID: 11160820, PMCID: PMC30565, ISSN: 1059-1524.

Entingh AJ, Law BK, Moses HL. Induction of the C/EBP homologous protein (CHOP) by amino acid deprivation requires insulin-like growth factor I, phosphatidylinositol 3-kinase, and mammalian target of rapamycin signaling. Endocrinology. 2001 Jan; 142(1): 221-8. PMID: 11145585, DOI: 10.1210/endo.142.1.7906, ISSN: 0013-7227.

Datta PK, Blake MC, Moses HL. Regulation of plasminogen activator inhibitor-1 expression by transforming growth factor-beta -induced physical and functional interactions between smads and Sp1. J. Biol. Chem. 2000 Dec 12/22/2000; 275(51): 40014-9. PMID: 11054406, PII: C000508200, DOI: 10.1074/jbc.C000508200, ISSN: 0021-9258.

Law BK, Waltner-Law ME, Entingh AJ, Chytil A, Aakre ME, Nørgaard P, Moses HL. Salicylate-induced growth arrest is associated with inhibition of p70s6k and down-regulation of c-myc, cyclin D1, cyclin A, and proliferating cell nuclear antigen. J. Biol. Chem. 2000 Dec 12/8/2000; 275(49): 38261-7. PMID: 10993886, PII: M005545200, DOI: 10.1074/jbc.M005545200, ISSN: 0021-9258.

Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL, Arteaga CL. Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J. Biol. Chem. 2000 Nov 11/24/2000; 275(47): 36803-10. PMID: 10969078, PII: M005912200, DOI: 10.1074/jbc.M005912200, ISSN: 0021-9258.

Datta PK, Moses HL. STRAP and Smad7 synergize in the inhibition of transforming growth factor beta signaling. Mol. Cell. Biol. 2000 May; 20(9): 3157-67. PMID: 10757800, PMCID: PMC85610, ISSN: 0270-7306.

Law BK, Norgaard P, Moses HL. Farnesyltransferase inhibitor induces rapid growth arrest and blocks p70s6k activation by multiple stimuli. J. Biol. Chem. 2000 Apr 4/14/2000; 275(15): 10796-801. PMID: 10753872, ISSN: 0021-9258.

Engel ME, McDonnell MA, Law BK, Moses HL. Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription. J. Biol. Chem. 1999 Dec 12/24/1999; 274(52): 37413-20. PMID: 10601313, ISSN: 0021-9258.

Saha D, Datta PK, Sheng H, Morrow JD, Wada M, Moses HL, Beauchamp RD. Synergistic induction of cyclooxygenase-2 by transforming growth factor-beta1 and epidermal growth factor inhibits apoptosis in epithelial cells. Neoplasia. 1999 Dec; 1(6): 508-17. PMID: 10935498, PMCID: PMC1508120, ISSN: 1522-8002.

Joseph H, Gorska AE, Sohn P, Moses HL, Serra R. Overexpression of a kinase-deficient transforming growth factor-beta type II receptor in mouse mammary stroma results in increased epithelial branching. Mol. Biol. Cell. 1999 Apr; 10(4): 1221-34. PMID: 10198068, PMCID: PMC25256, ISSN: 1059-1524.

Law BK, Nørgaard P, Gnudi L, Kahn BB, Poulson HS, Moses HL. Inhibition of DNA synthesis by a farnesyltransferase inhibitor involves inhibition of the p70(s6k) pathway. J. Biol. Chem. 1999 Feb 2/19/1999; 274(8): 4743-8. PMID: 9988711, ISSN: 0021-9258.

Nørgaard P, Law BK, Plovisson HS, Moses HL. Farnesyltransferase inhibitor-induced regression of mammary tumors in TGF alpha and TGF alpha/neu transgenic mice correlates with inhibition of map kinase and p70s6 kinase phosphorylation. Ann. N. Y. Acad. Sci. 1999; 886: 265-8. PMID: 10667235, ISSN: 0077-8923.

Nørgaard P, Law B, Joseph H, Page DL, Shyr Y, Mays D, Pietenpol JA, Kohl NE, Oliff A, Coffey RJ, Poulsen HS, Moses HL. Treatment with farnesyl-protein transferase inhibitor induces regression of mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis. Clin. Cancer Res. 1999 Jan; 5(1): 35-42. PMID: 9918200, ISSN: 1078-0432.

Datta PK, Chytil A, Gorska AE, Moses HL. Identification of STRAP, a novel WD domain protein in transforming growth factor-beta signaling. J. Biol. Chem. 1998 Dec 12/25/1998; 273(52): 34671-4. PMID: 9856985, ISSN: 0021-9258.

Alexandrow MG, Moses HL. C-myc-enhanced S phase entry in keratinocytes is associated with positive and negative effects on cyclin-dependent kinases. J. Cell. Biochem. 1998 Sep 9/15/1998; 70(4): 528-42. PMID: 9712150, PII: 10.1002/(SICI)1097-4644(19980915)70:4<528::AID-JCB9>3.0.CO;2-L, ISSN: 0730-2312.

Engel ME, Datta PK, Moses HL. RhoB is stabilized by transforming growth factor beta and antagonizes transcriptional activation. J. Biol. Chem. 1998 Apr 4/17/1998; 273(16): 9921-6. PMID: 9545335, ISSN: 0021-9258.

Gorska AE, Joseph H, Derynck R, Moses HL, Serra R. Dominant-negative interference of the transforming growth factor beta type II receptor in mammary gland epithelium results in alveolar hyperplasia and differentiation in virgin mice. Cell Growth Differ. 1998 Mar; 9(3): 229-38. PMID: 9543389, ISSN: 1044-9523.

Engel ME, Datta PK, Moses HL. Signal transduction by transforming growth factor-beta: a cooperative paradigm with extensive negative regulation. J. Cell. Biochem. Suppl. 1998; 30-31: 111-22. PMID: 9893262, ISSN: 0733-1959.

Serra R, Johnson M, Filvaroff EH, LaBorde J, Sheehan DM, Derynck R, Moses HL. Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J. Cell Biol. 1997 Oct 10/20/1997; 139(2): 541-52. PMID: 9334355, PMCID: PMC2139797, ISSN: 0021-9525.

Alexandrow MG, Moses HL. Kips off to Myc: implications for TGF beta signaling. J. Cell. Biochem. 1997 Sep 9/15/1997; 66(4): 427-32. PMID: 9282320, PII: 10.1002/(SICI)1097-4644(19970915)66:4<427::AID-JCB1>3.0.CO;2-N, ISSN: 0730-2312.

Arteaga CL, Moses HL. TGF-beta in mammary development and neoplasia. J Mammary Gland Biol Neoplasia. 1996 Oct; 1(4): 327-9. PMID: 10887506, ISSN: 1083-3021.

Moses HL, Serra R. Regulation of differentiation by TGF-beta. Curr. Opin. Genet. Dev. 1996 Oct; 6(5): 581-6. PMID: 8939725, ISSN: 0959-437X.

Holt JT, Arteaga CB, Robertson D, Moses HL. Gene therapy for the treatment of metastatic breast cancer by in vivo transduction with breast-targeted retroviral vector expressing antisense c-fos RNA. Hum. Gene Ther. 1996 Jul 7/10/1996; 7(11): 1367-80. PMID: 8818724, DOI: 10.1089/hum.1996.7.11-1367, ISSN: 1043-0342.

Serra R, Moses HL. Tumor suppressor genes in the TGF-beta signaling pathway?. Nat. Med. 1996 Apr; 2(4): 390-1. PMID: 8597940, ISSN: 1078-8956.

Kawabata M, Imamura T, Miyazono K, Engel ME, Moses HL. Interaction of the transforming growth factor-beta type I receptor with farnesyl-protein transferase-alpha. J. Biol. Chem. 1995 Dec 12/15/1995; 270(50): 29628-31. PMID: 8530343, ISSN: 0021-9258.

Alexandrow MG, Moses HL. Transforming growth factor beta 1 inhibits mouse keratinocytes late in G1 independent of effects on gene transcription. Cancer Res. 1995 Sep 9/1/1995; 55(17): 3928-32. PMID: 7641212, ISSN: 0008-5472.

Serra R, Moses HL. PRb is necessary for inhibition of N-myc expression by TGF-beta 1 in embryonic lung organ cultures. Development. 1995 Sep; 121(9): 3057-66. PMID: 7555731, ISSN: 0950-1991.

Pierce DF, Gorska AE, Chytil A, Meise KS, Page DL, Coffey RJ, Moses HL. Mammary tumor suppression by transforming growth factor beta 1 transgene expression. Proc. Natl. Acad. Sci. U.S.A. 1995 May 5/9/1995; 92(10): 4254-8. PMID: 7753792, PMCID: PMC41922, ISSN: 0027-8424.

Alexandrow MG, Kawabata M, Aakre M, Moses HL. Overexpression of the c-Myc oncoprotein blocks the growth-inhibitory response but is required for the mitogenic effects of transforming growth factor beta 1. Proc. Natl. Acad. Sci. U.S.A. 1995 Apr 4/11/1995; 92(8): 3239-43. PMID: 7724545, PMCID: PMC42141, ISSN: 0027-8424.

Alexandrow MG, Moses HL. Transforming growth factor beta and cell cycle regulation. Cancer Res. 1995 Apr 4/1/1995; 55(7): 1452-7. PMID: 7882352, ISSN: 0008-5472.

Kawabata M, Chytil A, Moses HL. Cloning of a novel type II serine/threonine kinase receptor through interaction with the type I transforming growth factor-beta receptor. J. Biol. Chem. 1995 Mar 3/10/1995; 270(10): 5625-30. PMID: 7890683, ISSN: 0021-9258.

Dagnino L, Zhu L, Skorecki KL, Moses HL. E2F-independent transcriptional repression by p107, a member of the retinoblastoma family of proteins. Cell Growth Differ. 1995 Feb; 6(2): 191-8. PMID: 7756178, ISSN: 1044-9523.

Chen, R.-H., Moses, H.L., Maruoka, E.M., Derynck, R., and Kawabata, M. Phosphorylation-dependent interaction of the cytoplasmic domains of the type I and type II transforming growth factor-? receptors. J. Biol. Chem. 1995; 270: 12235-41.

Satterwhite DJ, Aakre ME, Gorska AE, Moses HL. Inhibition of cell growth by TGF beta 1 is associated with inhibition of B-myb and cyclin A in both BALB/MK and Mv1Lu cells. Cell Growth Differ. 1994 Aug; 5(8): 789-99. PMID: 7986745, ISSN: 1044-9523.

Serra R, Pelton RW, Moses HL. TGF beta 1 inhibits branching morphogenesis and N-myc expression in lung bud organ cultures. Development. 1994 Aug; 120(8): 2153-61. PMID: 7523056, ISSN: 0950-1991.

Moses HL, Arteaga CL, Alexandrow MG, Dagnino L, Kawabata M, Pierce DF, Serra R. TGF beta regulation of cell proliferation. Int. Symp. Princess Takamatsu Cancer Res. Fund. 1994; 24: 250-63. PMID: 8983080.

Satterwhite DJ, Moses HL. Mechanisms of transforming growth factor-beta 1-induced cell cycle arrest. Invasion Metastasis. 1994; 14(1-6): 309-18. PMID: 7657524, ISSN: 0251-1789.

Pierce DF, Johnson MD, Matsui Y, Robinson SD, Gold LI, Purchio AF, Daniel CW, Hogan BL, Moses HL. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Genes Dev. 1993 Dec; 7(12A): 2308-17. PMID: 8253379, ISSN: 0890-9369.

Levine JH, Moses HL, Gold LI, Nanney LB. Spatial and temporal patterns of immunoreactive transforming growth factor beta 1, beta 2, and beta 3 during excisional wound repair. Am. J. Pathol. 1993 Aug; 143(2): 368-80. PMID: 8342593, PMCID: PMC1887040, ISSN: 0002-9440.

Johnson MD, Jennings MT, Gold LI, Moses HL. Transforming growth factor-beta in neural embryogenesis and neoplasia. Hum. Pathol. 1993 May; 24(5): 457-62. PMID: 8387957, ISSN: 0046-8177.

Arteaga CL, Carty-Dugger T, Moses HL, Hurd SD, Pietenpol JA. Transforming growth factor beta 1 can induce estrogen-independent tumorigenicity of human breast cancer cells in athymic mice. Cell Growth Differ. 1993 Mar; 4(3): 193-201. PMID: 8466857, ISSN: 1044-9523.

Dagnino L, Pietenpol JA, Yang EY, Moses HL. Transforming growth factor regulation of keratinocyte growth. Recent Results Cancer Res. 1993; 128: 15-29. PMID: 8356316, ISSN: 0080-0015.

Johnson MD, Gold LI, Moses HL. Evidence for transforming growth factor-beta expression in human leptomeningeal cells and transforming growth factor-beta-like activity in human cerebrospinal fluid. Lab. Invest. 1992 Sep; 67(3): 360-8. PMID: 1328762, ISSN: 0023-6837.

Johnson MD, Federspiel CF, Gold LI, Moses HL. Transforming growth factor-beta and transforming growth factor beta-receptor expression in human meningioma cells. Am. J. Pathol. 1992 Sep; 141(3): 633-42. PMID: 1325741, PMCID: PMC1886701, ISSN: 0002-9440.

Moses HL. TGF-beta regulation of epithelial cell proliferation. Mol. Reprod. Dev. 1992 Jun; 32(2): 179-84. PMID: 1637556, DOI: 10.1002/mrd.1080320215, ISSN: 1040-452X.

Pelton RW, Johnson MD, Perkett EA, Gold LI, Moses HL. Expression of transforming growth factor-beta 1, -beta 2, and -beta 3 mRNA and protein in the murine lung. Am. J. Respir. Cell Mol. Biol. 1991 Dec; 5(6): 522-30. PMID: 1958379, DOI: 10.1165/ajrcmb/5.6.522, ISSN: 1044-1549.

Barnard JA, Polk WH, Moses HL, Coffey RJ. Production of transforming growth factor-alpha by normal rat small intestine. Am. J. Physiol. 1991 Dec; 261(6 Pt 1): C994-1000. PMID: 1767826, ISSN: 0002-9513.

Lyons RM, Miller DA, Graycar JL, Moses HL, Derynck R. Differential binding of transforming growth factor-beta 1, -beta 2, and -beta 3 by fibroblasts and epithelial cells measured by affinity cross-linking of cell surface receptors. Mol. Endocrinol. 1991 Dec; 5(12): 1887-96. PMID: 1665203, DOI: 10.1210/mend-5-12-1887, ISSN: 0888-8809.

Pietenpol JA, Münger K, Howley PM, Stein RW, Moses HL. Factor-binding element in the human c-myc promoter involved in transcriptional regulation by transforming growth factor beta 1 and by the retinoblastoma gene product. Proc. Natl. Acad. Sci. U.S.A. 1991 Nov 11/15/1991; 88(22): 10227-31. PMID: 1946442, PMCID: PMC52901, ISSN: 0027-8424.

Pelton RW, Saxena B, Jones M, Moses HL, Gold LI. Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development. J. Cell Biol. 1991 Nov; 115(4): 1091-105. PMID: 1955457, PMCID: PMC2289937, ISSN: 0021-9525.

Schwartz HS, Butler MG, Jenkins RB, Miller DA, Moses HL. Telomeric associations and consistent growth factor overexpression detected in giant cell tumor of bone. Cancer Genet. Cytogenet. 1991 Oct 10/15/1991; 56(2): 263-76. PMID: 1756472, PII: 0165-4608(91)90179-X, ISSN: 0165-4608.

Jennings MT, Maciunas RJ, Carver R, Bascom CC, Juneau P, Misulis K, Moses HL. TGF beta 1 and TGF beta 2 are potential growth regulators for low-grade and malignant gliomas in vitro: evidence in support of an autocrine hypothesis. Int. J. Cancer. 1991 Aug 8/19/1991; 49(1): 129-39. PMID: 1874566, ISSN: 0020-7136.

Moses HL, Yang EY, Pietenpol JA. Regulation of epithelial proliferation by TGF-beta. Ciba Found. Symp. 1991; 157: 66-74; discussion 75. PMID: 2070684, ISSN: 0300-5208.

Moses HL, Pietenpol JA, Münger K, Murphy CS, Yang EY. TGF beta regulation of epithelial cell proliferation: role of tumor suppressor genes. Int. Symp. Princess Takamatsu Cancer Res. Fund. 1991; 22: 183-95. PMID: 1844240.

Murphy CS, Pietenpol JA, Münger K, Howley PM, Moses HL. C-myc and pRB: role in TGF-beta 1 inhibition of keratinocyte proliferation. Cold Spring Harb. Symp. Quant. Biol. 1991; 56: 129-35. PMID: 1819482, ISSN: 0091-7451.

Pelton RW, Moses HL. The beta-type transforming growth factor. Mediators of cell regulation in the lung. Am. Rev. Respir. Dis. 1990 Dec; 142(6 Pt 2): S31-5. PMID: 2174660, DOI: 10.1164/ajrccm/142.6_Pt_2.S31, ISSN: 0003-0805.

Fava RA, Casey TT, Wilcox J, Pelton RW, Moses HL, Nanney LB. Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules. Blood. 1990 Nov 11/15/1990; 76(10): 1946-55. PMID: 2242422, ISSN: 0006-4971.

Perkett EA, Lyons RM, Moses HL, Brigham KL, Meyrick B. Transforming growth factor-beta activity in sheep lung lymph during the development of pulmonary hypertension. J. Clin. Invest. 1990 Nov; 86(5): 1459-64. PMID: 2243124, PMCID: PMC296890, DOI: 10.1172/JCI114862, ISSN: 0021-9738.

Moses HL, Yang EY, Pietenpol JA. TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights. Cell. 1990 Oct 10/19/1990; 63(2): 245-7. PMID: 2208284, PII: 0092-8674(90)90155-8, ISSN: 0092-8674.

Pelton RW, Dickinson ME, Moses HL, Hogan BL. In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2. Development. 1990 Oct; 110(2): 609-20. PMID: 1723948, ISSN: 0950-1991.

Pelton RW, Hogan BL, Miller DA, Moses HL. Differential expression of genes encoding TGFs beta 1, beta 2, and beta 3 during murine palate formation. Dev. Biol. 1990 Oct; 141(2): 456-60. PMID: 1698672, PII: 0012-1606(90)90401-4, ISSN: 0012-1606.

Arteaga CL, Coffey RJ, Dugger TC, McCutchen CM, Moses HL, Lyons RM. Growth stimulation of human breast cancer cells with anti-transforming growth factor beta antibodies: evidence for negative autocrine regulation by transforming growth factor beta. Cell Growth Differ. 1990 Aug; 1(8): 367-74. PMID: 2177634, ISSN: 1044-9523.

Yang EY, Moses HL. Transforming growth factor beta 1-induced changes in cell migration, proliferation, and angiogenesis in the chicken chorioallantoic membrane. J. Cell Biol. 1990 Aug; 111(2): 731-41. PMID: 1696268, PMCID: PMC2116177, ISSN: 0021-9525.

Beauchamp RD, Lyons RM, Yang EY, Coffey RJ, Moses HL. Expression of and response to growth regulatory peptides by two human pancreatic carcinoma cell lines. Pancreas. 1990 Jul; 5(4): 369-80. PMID: 2199964, ISSN: 0885-3177.

Barnard JA, Lyons RM, Moses HL. The cell biology of transforming growth factor beta. Biochim. Biophys. Acta. 1990 Jun 6/1/1990; 1032(1): 79-87. PMID: 2194569, PII: 0304-419X(90)90013-Q, ISSN: 0006-3002.

Pietenpol JA, Stein RW, Moran E, Yaciuk P, Schlegel R, Lyons RM, Pittelkow MR, Münger K, Howley PM, Moses HL. TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains. Cell. 1990 Jun 6/1/1990; 61(5): 777-85. PMID: 2140528, PII: 0092-8674(90)90188-K, ISSN: 0092-8674.

Pietenpol JA, Holt JT, Stein RW, Moses HL. Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. Proc. Natl. Acad. Sci. U.S.A. 1990 May; 87(10): 3758-62. PMID: 2187192, PMCID: PMC53982, ISSN: 0027-8424.

Sipes NJ, Miller DA, Bascom CC, Winkler JK, Matrisian LM, Moses HL. Altered regulation of protein disulfide isomerase in cells resistant to the growth-inhibitory effects of transforming growth factor beta 1. Cell Growth Differ. 1990 May; 1(5): 241-6. PMID: 2085467, ISSN: 1044-9523.

Lyons RM, Gentry LE, Purchio AF, Moses HL. Mechanism of activation of latent recombinant transforming growth factor beta 1 by plasmin. J. Cell Biol. 1990 Apr; 110(4): 1361-7. PMID: 2139036, PMCID: PMC2116088, ISSN: 0021-9525.

Lyons RM, Moses HL. Transforming growth factors and the regulation of cell proliferation. Eur. J. Biochem. 1990 Feb 2/14/1990; 187(3): 467-73. PMID: 2406131, ISSN: 0014-2956.

Miller DA, Pelton RW, Derynck R, Moses HL. Transforming growth factor-beta. A family of growth regulatory peptides. Ann. N. Y. Acad. Sci. 1990; 593: 208-17. PMID: 2375595, ISSN: 0077-8923.

Sipes NJ, Lyons RM, Moses HL. Isolation and characterization of Kirsten murine sarcoma virus-transformed mouse keratinocytes resistant to transforming growth factor beta. Mol. Carcinog. 1990; 3(1): 12-9. PMID: 2157456, ISSN: 0899-1987.

Miller DA, Lee A, Matsui Y, Chen EY, Moses HL, Derynck R. Complementary DNA cloning of the murine transforming growth factor-beta 3 (TGF beta 3) precursor and the comparative expression of TGF beta 3 and TGF beta 1 messenger RNA in murine embryos and adult tissues. Mol. Endocrinol. 1989 Dec; 3(12): 1926-34. PMID: 2628730, DOI: 10.1210/mend-3-12-1926, ISSN: 0888-8809.

Bascom CC, Wolfshohl JR, Coffey RJ, Madisen L, Webb NR, Purchio AR, Derynck R, Moses HL. Complex regulation of transforming growth factor beta 1, beta 2, and beta 3 mRNA expression in mouse fibroblasts and keratinocytes by transforming growth factors beta 1 and beta 2. Mol. Cell. Biol. 1989 Dec; 9(12): 5508-15. PMID: 2586525, PMCID: PMC363721, ISSN: 0270-7306.

Pelton RW, Nomura S, Moses HL, Hogan BL. Expression of transforming growth factor beta 2 RNA during murine embryogenesis. Development. 1989 Aug; 106(4): 759-67. PMID: 2485246, ISSN: 0950-1991.

Miller DA, Lee A, Pelton RW, Chen EY, Moses HL, Derynck R. Murine transforming growth factor-beta 2 cDNA sequence and expression in adult tissues and embryos. Mol. Endocrinol. 1989 Jul; 3(7): 1108-14. PMID: 2797004, DOI: 10.1210/mend-3-7-1108, ISSN: 0888-8809.

Skinner MK, Moses HL. Transforming growth factor beta gene expression and action in the seminiferous tubule: peritubular cell-Sertoli cell interactions. Mol. Endocrinol. 1989 Apr; 3(4): 625-34. PMID: 2725526, DOI: 10.1210/mend-3-4-625, ISSN: 0888-8809.

Barnard JA, Beauchamp RD, Coffey RJ, Moses HL. Regulation of intestinal epithelial cell growth by transforming growth factor type beta. Proc. Natl. Acad. Sci. U.S.A. 1989 Mar; 86(5): 1578-82. PMID: 2466294, PMCID: PMC286741, ISSN: 0027-8424.

Bascom CC, Sipes NJ, Coffey RJ, Moses HL. Regulation of epithelial cell proliferation by transforming growth factors. J. Cell. Biochem. 1989 Jan; 39(1): 25-32. PMID: 2654145, DOI: 10.1002/jcb.240390104, ISSN: 0730-2312.

Barnard JA, Bascom CC, Lyons RM, Sipes NJ, Moses HL. Transforming growth factor beta in the control of epidermal proliferation. Am. J. Med. Sci. 1988 Sep; 296(3): 159-63. PMID: 2459967, ISSN: 0002-9629.

Coffey RJ, Bascom CC, Sipes NJ, Graves-Deal R, Weissman BE, Moses HL. Selective inhibition of growth-related gene expression in murine keratinocytes by transforming growth factor beta. Mol. Cell. Biol. 1988 Aug; 8(8): 3088-93. PMID: 2463471, PMCID: PMC363535, ISSN: 0270-7306.

Lyons RM, Keski-Oja J, Moses HL. Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J. Cell Biol. 1988 May; 106(5): 1659-65. PMID: 2967299, PMCID: PMC2115066, ISSN: 0021-9525.

Coffey RJ, Sipes NJ, Bascom CC, Graves-Deal R, Pennington CY, Weissman BE, Moses HL. Growth modulation of mouse keratinocytes by transforming growth factors. Cancer Res. 1988 Mar 3/15/1988; 48(6): 1596-602. PMID: 2449957, ISSN: 0008-5472.

Keski-Oja J, Raghow R, Sawdey M, Loskutoff DJ, Postlethwaite AE, Kang AH, Moses HL. Regulation of mRNAs for type-1 plasminogen activator inhibitor, fibronectin, and type I procollagen by transforming growth factor-beta. Divergent responses in lung fibroblasts and carcinoma cells. J. Biol. Chem. 1988 Mar 3/5/1988; 263(7): 3111-5. PMID: 3125175, ISSN: 0021-9258.

Keski-Oja J, Blasi F, Leof EB, Moses HL. Regulation of the synthesis and activity of urokinase plasminogen activator in A549 human lung carcinoma cells by transforming growth factor-beta. J. Cell Biol. 1988 Feb; 106(2): 451-9. PMID: 3276718, PMCID: PMC2114980, ISSN: 0021-9525.

Keski-Oja J, Postlethwaite AE, Moses HL. Transforming growth factors in the regulation of malignant cell growth and invasion. Cancer Invest. 1988; 6(6): 705-24. PMID: 3072995, ISSN: 0735-7907.

Keski-Oja J, Lyons RM, Moses HL. Immunodetection and modulation of cellular growth with antibodies against native transforming growth factor-beta 1. Cancer Res. 1987 Dec 12/15/1987; 47(24 Pt 1): 6451-8. PMID: 2890433, ISSN: 0008-5472.

Moses HL, Coffey RJ, Leof EB, Lyons RM, Keski-Oja J. Transforming growth factor beta regulation of cell proliferation. J Cell Physiol Suppl. 1987; Suppl 5: 1-7. PMID: 3316252, ISSN: 0737-1462.