Skip to main content
SpringerLink
Log in

The multifunctional role of transforming growth factor (TGF)-ßs on mammary epithelial cell biology

  • Tumor growth pathways and their inhibition
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

The transforming growth factor-βs are potent growth inhibitors of normal and transformed breast epithelial cells in culture. In vivo, these peptides modulate the development of the mouse mammary gland. Tissuespecific overexpression of mature TGF-β1 in transgenic mice results in mammary gland atrophy and prevention of carcinogen-induced breast tumorigenesis. However, the inhibitory effect of endogenous or exogenous TGF-βs on established tumor cells is less clear. Several published circumstantial and more direct data argue that, in some cases, the tumor cell TGF-βs may contribute to the maintenance and/or progression of tumor cells in an intact host by modulating their interaction with host factors. This differential role of the TGF-βs on mammary cells as determined by their normal or transformed phenotype as well as the biological and clinical implications of these data are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Moses HL, Branum EB, Proper JA, et al: Transforming growth factor production by chemically transformed cells. Cancer Res 41:2842–2848, 1981

    PubMed  Google Scholar 

  2. Roberts AB, Anzano MA, Lamb LC, et al: New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci USA 78:5339–5343, 1981

    PubMed  Google Scholar 

  3. Roberts AB, Sporn MB: The transforming growth factor-βs.In: Sporn MB, Roberts AB (eds) Handbook of Experimental Pharmacology, vol 95. Springer-Verlag, Heidelberg, 1990, pp 419–472

    Google Scholar 

  4. Moses HL: The biological action of transforming growth factor β.In: Sara V, Hall K, Low H (eds) Growth Factors from Genes to Clinical Application. Raven Press, New York, 1990, pp 141–155

    Google Scholar 

  5. Moses HL, Yang EY, Pietenpol JA: TGF-β stimulation and inhibition of cell proliferation: New mechanistic insights. Cell 63:245–247, 1990

    PubMed  Google Scholar 

  6. Miller DA, Pelton RW, Derynck R, et al: Transforming growth factor-β: A family of growth regulatory peptides. Ann NY Acad Sci 593:208–217, 1990

    PubMed  Google Scholar 

  7. Pelton RW, Saxena B, Jones M, et al: Immunohistochemical localization of TGF-β1, TGF-β2, and TGF-β3 in the mouse embryo: Expression patterns suggest multiple roles during embryonic development. J Cell Biol 115:1091–1105, 1991

    PubMed  Google Scholar 

  8. Lyons RM, Moses HL: Transforming growth factors and the regulation of cell proliferation. Eur J Biochem 187:467–473, 1990

    PubMed  Google Scholar 

  9. Robinson SD, Silberstein GB, Roberts AB, et al: Regulated expression and growth inhibitory effects of transforming growth factor-β isoforms in mouse mammary gland development. Development 113:867–878, 1991

    PubMed  Google Scholar 

  10. Silberstein GB, Daniel CW: Reversible inhibition of mammary gland growth by transforming growth factor-β. Science 237:291–293, 1987

    PubMed  Google Scholar 

  11. Silberstein GB, Strickland P, Coleman S, et al: Epithelium-dependent extracellular matrix synthesis in transforming growth factor-β1 growth-inhibited mouse mammary gland. J Cell Biol 110:2209–2219, 1990

    PubMed  Google Scholar 

  12. Daniel CW, Silberstein GB, Van Horn K, et al: TGF-β1-induced growth inhibition of mouse mammary ductal growth: Development specificity and characterization. Dev Biol 135:20–30, 1989

    PubMed  Google Scholar 

  13. Gomm JJ, Smith J, Ryall GK, et al: Localization of basic fibroblast growth factor and transforming growth factor β1 in the human mammary gland. Cancer Res 51:4685–4692, 1991

    PubMed  Google Scholar 

  14. McCune BK, Mullin BR, Flanders KC, et al: Localization of transforming growth-β isotypes in lesions of the human breast. Human Pathol 23:13–20, 1992

    Google Scholar 

  15. Pierce DF, Johnson MD, Matsui Y, et al: Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-β1. Genes Dev 7:2308–2317, 1993

    PubMed  Google Scholar 

  16. Jhappan C, Geiser AG, Kordon EC, et al: Targeting of a transforming growth factor β1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. EMBO J 12:1835–1845, 1993

    PubMed  Google Scholar 

  17. Zajchowski D, Band V, Pauzie N, et al: Expression of growth factors and oncogenes in normal and tumorderived human mammary epithelial cells. Cancer Res 48:7041–7047, 1988

    PubMed  Google Scholar 

  18. Valverius EM, Walker-Jones D, Bates SE, et al: Production of and responsiveness to transforming growth factor-β in normal and oncogene-transformed human mammary epithelial cells. Cancer Res 49: 6269–6274, 1989

    PubMed  Google Scholar 

  19. Dickson RB, Bates SE, McManaway ME, et al: Characterization of estrogen responsive transforming activity in human breast cancer cell lines. Cancer Res 46:1707–1713, 1986

    PubMed  Google Scholar 

  20. Arrick BA, Korc M, Derynck R: Differential regulation of expression of three transforming growth factor β species in human breast cancer cell lines by estradiol. Cancer Res 50:299–303, 1990

    PubMed  Google Scholar 

  21. Knabbe C, Lippman ME, Wakefield LM, et al: Evidence that transforming growth factor-β is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48:417–428, 1987

    PubMed  Google Scholar 

  22. Arteaga CL, Tandon AK, Von Hoff DD, et al: Transforming growth factor β: A potential autocrine growth inhibitor of estrogen receptor-negative human breast cancer cells. Cancer Res 48:3898–3904, 1988

    PubMed  Google Scholar 

  23. Zugmaier G, Ennis BW, Deschauer B, et al: Transforming growth factors type β1 and β2 are equipotent growth inhibitors of human breast cancer cell lines. J Cell Physiol 141:353–361, 1989

    PubMed  Google Scholar 

  24. Jeng M-H, Jordan VC: Growth stimulation and differential regulation of transforming growth factor-β1 (TGF-β1), TGF-β2, and TGF-β3 messenger RNA levels by norethindrone in MCF-7 human breast cancer cells. Mol Endocrinol 5:1120–1128, 1991

    PubMed  Google Scholar 

  25. Warri AM, Huovinen RL, Laine AM, et al: Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vitro and in vivo. J Natl Cancer Inst 85:1412–1418, 1993

    PubMed  Google Scholar 

  26. Colletta AA, Wakefield LM, Howell FV, et al: The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor β. J Clin Invest 87:277–283, 1991

    PubMed  Google Scholar 

  27. Arteaga CL, Coffey RJ, Dugger TC, et al: Growth stimulation of human breast cancer cells with antitransforming growth factor β antibodies: evidence for negative autocrine growth regulation by transforming growth factor β. Cell Growth & Differ 1:367–374, 1990

    Google Scholar 

  28. Butta A, MacLennan K, Flanders KC, et al: Induction of transforming growth factor β1 in human breast cancer in vivo following tamoxifen treatment. Cancer Res 52:4261–4264, 1992

    PubMed  Google Scholar 

  29. Karey KP, Sirbasku DA: Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17β-estradiol. Cancer Res 48: 4083–4092, 1988

    PubMed  Google Scholar 

  30. Murphy LC, Dotzlaw H: Regulation of transforming growth factor α and transforming growth factor α messenger ribonucleic acid abundance in T-47D human breast cancer cells. Mol Endocrinol 3:611–617, 1989

    PubMed  Google Scholar 

  31. Wrana JL, Attisano L, Carcamo J, et al: TGFβ signals through a heteromeric protein kinase receptor complex. Cell 71:1003–1014, 1992

    PubMed  Google Scholar 

  32. Chen R-H, Ebner R, Derynck R: Inactivation of the type II receptor reveals two receptor pathways for diverse TGF-β activities. Science 260:1335–1338, 1993

    PubMed  Google Scholar 

  33. Inagaki M, Moustakas M, Lin HY, et al: Growth inhibition by transforming growth factor ß (TGF-ß) type I receptor is restored in TGF-ß-resistant hepatoma cells after expression of TGF-ß receptor type II cDNA. Proc Natl Acad Sci USA 90:5359–5363, 1993

    PubMed  Google Scholar 

  34. Sun L, Wu G, Willson JKV, et al: Expression of transforming growth factor β type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem 269:26449–26455, 1994

    PubMed  Google Scholar 

  35. Dugger TC, Meggouh F, Arteaga CL: Blockade of TGF-ß1, -ß2, and -ß3 does not abrogate tamoxifeninduced growth inhibition of human breast carcinoma cells. Proc Amer Assoc Cancer Res 35:265, 1994

    Google Scholar 

  36. Dickson RB, Kasid A, Huff KK, et al: Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17β-estradiol or v-Ha-ras oncogene. Proc Natl Acad Sci USA 84:837–841, 1987

    PubMed  Google Scholar 

  37. Kasid A, Knabbe C, Lippman ME: Effect of v-rasH oncogene transfection on estrogen-independent tumorigenicity of estrogen-dependent human breast cancer cells. Cancer Res 47:5733–5738, 1987

    PubMed  Google Scholar 

  38. Daly RJ, King RJB, Darbre PD: Interaction of growth factors during progression towards steroid independence in T-47-D human breast cancer cells. J Cell Biochem 43:199–211, 1990

    PubMed  Google Scholar 

  39. Barrett-Lee P, Travers M, Luqmani Y, et al: Transcripts for transforming growth factors in human breast cancer: clinical correlates. Br J Cancer 61:612–617, 1990

    PubMed  Google Scholar 

  40. King RJB, Wang DY, Daly RJ, et al: Approaches to studying the role of growth factors in the progression of breast tumors from the steroid sensitive to insensitive state. J Steroid Biochem 34:133–138, 1989

    PubMed  Google Scholar 

  41. MacCallum J, Bartlett JMS, Thompson AM, et al: Expression of transforming growth beta mRNA isoforms in human breast cancer. Br J Cancer 69:1006–1009, 1994

    PubMed  Google Scholar 

  42. Welch DR, Fabra A, Nakajima M: Transforming growth factor β stimulates mammary adenocarcinoma cell invasion and metastatic potential. Proc Natl Acad Sci USA 87:7678–7682, 1990

    PubMed  Google Scholar 

  43. Walker RA, Dearing SJ: Transforming growth factor beta-1 in ductal carcinoma in situ and invasive carcinomas of the breast. Eur J Cancer 28:641–644, 1992

    PubMed  Google Scholar 

  44. Walker RJ, Dearing SJ, Gallacher B: Relationship of transforming growth factor β1 to extracellular matrix and stromal infiltrates in invasive breast carcinoma. Br J Cancer 69:1160–1165, 1994

    PubMed  Google Scholar 

  45. Gorsch SM, Memoli VA, Stukel TA, et al: Immunohistochemical staining for transforming growth factor β1 associates with disease progression in human breast cancer. Cancer Res 52:6949–6952, 1992

    PubMed  Google Scholar 

  46. Thompson AM, Kerr DJ, Steel CM: Transforming growth factor β1 is implicated in the failure of tamoxifen therapy in human breast cancer. Br J Cancer 63:609–614, 1991

    PubMed  Google Scholar 

  47. Zugmaier G, Paik S, Wilding G, et al: Transforming growth factor β1 induces cachexia and systemic fibrosis without an antitumor effect in nude mice. Cancer Res 51:3590–3594, 1991

    PubMed  Google Scholar 

  48. Arteaga CL, Carty-Dugger T, Moses HL, et al: Transforming growth factor β1 can induce estrogen-independent tumorigenicity of human breast cancer cells in athymic mice. Cell Growth & Differ 4:193–201, 1993

    Google Scholar 

  49. Lucas C, Bald LN, Fendly BM, et al: The autocrine production of transforming growth factor-β1 during lymphocyte activation: a study with a monoclonal antibody-based ELISA. J Immunol 145:1415–1422, 1990

    PubMed  Google Scholar 

  50. Arteaga CL, Hurd SD, Winnier AR, et al: Antitransforming growth factor (TGF)-β antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity: Implications for a possible role of tumor cell/host TGF-β interactions in human breast cancer progression. J Clin Invest 92: 2569–2576, 1993

    PubMed  Google Scholar 

  51. Pierce DF, Gorska AE, Chytil A, et al: Mammary tumor suppression by transforming growth factor ß1 transgene expression. Proc Natl Acad Sci USA 92: 4254–4258, 1995

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine and Cell Biology, Vanderbilt University School of Medicine, Nashville, TN, USA

    Carlos L. Arteaga, Teresa C. Dugger & Stephen D. Hurd

  2. Department of Veteran Affairs Medical Center, Nashville, TN, USA

    Carlos L. Arteaga, Teresa C. Dugger & Stephen D. Hurd

Authors
  1. Carlos L. Arteaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Teresa C. Dugger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stephen D. Hurd
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arteaga, C.L., Dugger, T.C. & Hurd, S.D. The multifunctional role of transforming growth factor (TGF)-ßs on mammary epithelial cell biology. Breast Cancer Res Tr 38, 49–56 (1996). https://doi.org/10.1007/BF01803783

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01803783

Key words

Search

Navigation