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. 1987 Feb;84(3):837–841. doi: 10.1073/pnas.84.3.837

Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene.

R B Dickson, A Kasid, K K Huff, S E Bates, C Knabbe, D Bronzert, E P Gelmann, M E Lippman
PMCID: PMC304311  PMID: 2880347

Abstract

The MCF-7 human breast cancer cell line responds to estrogen stimulation in vitro by increased secretion of growth factors and proliferation and in vivo by tumor formation in the nude mouse. To test a possible role of growth factor secretion in expression of the tumorigenic phenotype, we stably transfected MCF-7 cells with the v-Ha-ras oncogene to produce the MCF-7ras cell line. The MCF-7ras cell line was tumorigenic in the absence of estrogens and secreted 3- to 5-fold elevated levels of a high molecular weight form of a type alpha transforming growth factor-like growth factor, type beta transforming growth factor, and insulin-like growth factor I. MCF-7ras cells, in contrast to MCF-7, were less sensitive to further growth stimulation by estrogen, type alpha transforming growth factor, and insulin-like growth factor I and showed little change in receptor levels for these hormones. Conditioned medium from MCF-7ras cells as well as two of its component growth factors (insulin-like growth factor I and type alpha transforming growth factor) replaced estrogen in stimulating MCF-7 colony formation in vitro. A coordinate increase in growth factor secretion by human breast cancer may contribute to its escape from estrogen dependence.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoniades H. N., Scher C. D., Stiles C. D. Purification of human platelet-derived growth factor. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1809–1813. doi: 10.1073/pnas.76.4.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anzano M. A., Roberts A. B., De Larco J. E., Wakefield L. M., Assoian R. K., Roche N. S., Smith J. M., Lazarus J. E., Sporn M. B. Increased secretion of type beta transforming growth factor accompanies viral transformation of cells. Mol Cell Biol. 1985 Jan;5(1):242–247. doi: 10.1128/mcb.5.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anzano M. A., Roberts A. B., Smith J. M., Sporn M. B., De Larco J. E. Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type alpha and type beta transforming growth factors. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6264–6268. doi: 10.1073/pnas.80.20.6264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Assoian R. K., Grotendorst G. R., Miller D. M., Sporn M. B. Cellular transformation by coordinated action of three peptide growth factors from human platelets. 1984 Jun 28-Jul 4Nature. 309(5971):804–806. doi: 10.1038/309804a0. [DOI] [PubMed] [Google Scholar]
  5. Assoian R. K., Komoriya A., Meyers C. A., Miller D. M., Sporn M. B. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed] [Google Scholar]
  6. Bowen-Pope D. F., Vogel A., Ross R. Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2396–2400. doi: 10.1073/pnas.81.8.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brunk C. F., Jones K. C., James T. W. Assay for nanogram quantities of DNA in cellular homogenates. Anal Biochem. 1979 Jan 15;92(2):497–500. doi: 10.1016/0003-2697(79)90690-0. [DOI] [PubMed] [Google Scholar]
  8. Butler W. B., Kirkland W. L., Jorgensen T. L. Induction of plasminogen activator by estrogen in a human breast cancer cell line (MCF-7). Biochem Biophys Res Commun. 1979 Oct 29;90(4):1328–1334. doi: 10.1016/0006-291x(79)91181-1. [DOI] [PubMed] [Google Scholar]
  9. Danielpour D., Sirbasku D. A. New perspectives in hormone-dependent (responsive) and autonomous mammary tumor growth: role of autostimulatory growth factors. In Vitro. 1984 Dec;20(12):975–980. doi: 10.1007/BF02619670. [DOI] [PubMed] [Google Scholar]
  10. De Larco J. E., Preston Y. A., Todaro G. J. Properties of a sarcoma-growth-factor-like peptide from cells transformed by a temperature-sensitive sarcoma virus. J Cell Physiol. 1981 Oct;109(1):143–152. doi: 10.1002/jcp.1041090116. [DOI] [PubMed] [Google Scholar]
  11. De Larco J. E., Tadaro G. J. A human fibrosarcoma cell line producing multiplication stimulating activity (MSA)-related peptides. Nature. 1978 Mar 23;272(5651):356–358. doi: 10.1038/272356a0. [DOI] [PubMed] [Google Scholar]
  12. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  13. Dickson R. B., Bates S. E., McManaway M. E., Lippman M. E. Characterization of estrogen responsive transforming activity in human breast cancer cell lines. Cancer Res. 1986 Apr;46(4 Pt 1):1707–1713. [PubMed] [Google Scholar]
  14. Dickson R. B., Huff K. K., Spencer E. M., Lippman M. E. Induction of epidermal growth factor-related polypeptides by 17 beta-estradiol in MCF-7 human breast cancer cells. Endocrinology. 1986 Jan;118(1):138–142. doi: 10.1210/endo-118-1-138. [DOI] [PubMed] [Google Scholar]
  15. Dickson R. B., McManaway M. E., Lippman M. E. Estrogen-induced factors of breast cancer cells partially replace estrogen to promote tumor growth. Science. 1986 Jun 20;232(4757):1540–1543. doi: 10.1126/science.3715461. [DOI] [PubMed] [Google Scholar]
  16. Engel L. W., Young N. A. Human breast carcinoma cells in continuous culture: a review. Cancer Res. 1978 Nov;38(11 Pt 2):4327–4339. [PubMed] [Google Scholar]
  17. Frolik C. A., Wakefield L. M., Smith D. M., Sporn M. B. Characterization of a membrane receptor for transforming growth factor-beta in normal rat kidney fibroblasts. J Biol Chem. 1984 Sep 10;259(17):10995–11000. [PubMed] [Google Scholar]
  18. Furlanetto R. W., DiCarlo J. N. Somatomedin-C receptors and growth effects in human breast cells maintained in long-term tissue culture. Cancer Res. 1984 May;44(5):2122–2128. [PubMed] [Google Scholar]
  19. Gospodarowicz D., Greenburg G., Bialecki H., Zetter B. R. Factors involved in the modulation of cell proliferation in vivo and in vitro: the role of fibroblast and epidermal growth factors in the proliferative response of mammalian cells. In Vitro. 1978 Jan;14(1):85–118. doi: 10.1007/BF02618177. [DOI] [PubMed] [Google Scholar]
  20. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  21. Ham R. G., McKeehan W. L. Media and growth requirements. Methods Enzymol. 1979;58:44–93. doi: 10.1016/s0076-6879(79)58126-9. [DOI] [PubMed] [Google Scholar]
  22. Huff K. K., Kaufman D., Gabbay K. H., Spencer E. M., Lippman M. E., Dickson R. B. Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res. 1986 Sep;46(9):4613–4619. [PubMed] [Google Scholar]
  23. Kao R. T., Hall J., Engel L., Stern R. The matrix of human breast tumor cells is mitogenic for fibroblasts. Am J Pathol. 1984 Apr;115(1):109–116. [PMC free article] [PubMed] [Google Scholar]
  24. Kasid A., Lippman M. E., Papageorge A. G., Lowy D. R., Gelmann E. P. Transfection of v-rasH DNA into MCF-7 human breast cancer cells bypasses dependence on estrogen for tumorigenicity. Science. 1985 May 10;228(4700):725–728. doi: 10.1126/science.4039465. [DOI] [PubMed] [Google Scholar]
  25. Krupp M. N., Connolly D. T., Lane M. D. Synthesis, turnover, and down-regulation of epidermal growth factor receptors in human A431 epidermoid carcinoma cells and skin fibroblasts. J Biol Chem. 1982 Oct 10;257(19):11489–11496. [PubMed] [Google Scholar]
  26. Kurachi H., Okamoto S., Oka T. Evidence for the involvement of the submandibular gland epidermal growth factor in mouse mammary tumorigenesis. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5940–5943. doi: 10.1073/pnas.82.17.5940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lawrence D. A., Pircher R., Krycève-Martinerie C., Jullien P. Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol. 1984 Oct;121(1):184–188. doi: 10.1002/jcp.1041210123. [DOI] [PubMed] [Google Scholar]
  28. Lippman M. E. Efforts to combine endocrine and chemotherapy in the management of breast cancer: do two and two equal three? Breast Cancer Res Treat. 1983;3(2):117–127. doi: 10.1007/BF01803554. [DOI] [PubMed] [Google Scholar]
  29. Marquardt H., Wilson G. L., Todaro G. J. Isolation and characterization of a multiplication-stimulating activity (MSA)-like polypeptide produced by a human fibrosarcoma cell line. J Biol Chem. 1980 Oct 10;255(19):9177–9181. [PubMed] [Google Scholar]
  30. Massagué J., Kelly B., Mottola C. Stimulation by insulin-like growth factors is required for cellular transformation by type beta transforming growth factor. J Biol Chem. 1985 Apr 25;260(8):4551–4554. [PubMed] [Google Scholar]
  31. Osborne C. K., Hamilton B., Titus G., Livingston R. B. Epidermal growth factor stimulation of human breast cancer cells in culture. Cancer Res. 1980 Jul;40(7):2361–2366. [PubMed] [Google Scholar]
  32. Ozanne B., Fulton R. J., Kaplan P. L. Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell-line produce transforming factors. J Cell Physiol. 1980 Oct;105(1):163–180. doi: 10.1002/jcp.1041050118. [DOI] [PubMed] [Google Scholar]
  33. Roberts A. B., Anzano M. A., Wakefield L. M., Roche N. S., Stern D. F., Sporn M. B. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci U S A. 1985 Jan;82(1):119–123. doi: 10.1073/pnas.82.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Salomon D. S., Zwiebel J. A., Bano M., Losonczy I., Fehnel P., Kidwell W. R. Presence of transforming growth factors in human breast cancer cells. Cancer Res. 1984 Sep;44(9):4069–4077. [PubMed] [Google Scholar]
  35. Soule H. D., McGrath C. M. Estrogen responsive proliferation of clonal human breast carcinoma cells in athymic mice. Cancer Lett. 1980 Aug;10(2):177–189. doi: 10.1016/0304-3835(80)90042-7. [DOI] [PubMed] [Google Scholar]
  36. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  37. Twardzik D. R., Todaro G. J., Marquardt H., Reynolds F. H., Jr, Stephenson J. R. Transformation induced by Abelson murine leukemia virus involves production of a polypeptide growth factor. Science. 1982 May 21;216(4548):894–897. doi: 10.1126/science.6177040. [DOI] [PubMed] [Google Scholar]
  38. Vignon F., Derocq D., Chambon M., Rochefort H. Les protéines oestrogéno-induites sécrétées par les cellules mammaires cancéreuses humaines MCF7 stimulent leur prolifération. C R Seances Acad Sci III. 1983 Jan 24;296(3):151–156. [PubMed] [Google Scholar]

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