Breast Cancer Research and Treatment

, Volume 1, Issue 4, pp 381–389 | Cite as

Growth regulation of two rat adenocarcinoma cell lines by dexamethasone and progesterone

  • E. Joly
  • F. Vignon
  • H. Rochefort


We have studied the effect of steroids on cell proliferation in two continuous cell lines derived from rat mammary tumors induced by 7, 12-dimethyl-benz (a) anthracene (DMBA) and N-nitrosomethylurea (NMU). These cell lines contain high concentrations of glucocorticoid and androgen receptors but no estrogen and progesterone receptors as previously shown (1). The cell proliferation was evaluated by measuring [3H] thymidine incorporation into DNA, cell number, and DNA content. Dexamethasone was found to markedly stimulate cell proliferation in a dose-dependent manner, suggesting that it was acting via the glucocorticoid receptor. The effect of 5α-dihydrotestosterone (DHT) was weaker since a stimulation of [3H] thymidine incorporation was contrasted by the absence of a constant increase of cell proliferation. Progesterone partially stimulated NMU cell growth and totally inhibited the stimulatory effect of dexamethasone in both cell lines. The synthetic progestin R5020 displayed a similar activity to that of progesterone.

These results show that progestins can directly modulate the growth of mammary cancer cells even in the absence of progesterone receptor by interacting on the glucocorticoid receptor. We conclude that progestins act mostly as partial agonist-antagonists of glucocorticoids in these two rat mammary adenocarcinoma cell lines.


androgens glucocorticoids mammary cancer progestins tumor proliferation 


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  1. 1.
    Vignon F, Chan PC, Rochefort H: Hormonal regulation in two rat mammary cell lines: Glucocorticoid and androgen receptors. Mol Cell Endocrinology 13:191–202, 1979Google Scholar
  2. 2.
    Dao TL, Sinha D: Oestrogen and prolactin in mammary carcinogenesis,In AR Boyns and K Griffiths (eds): Alpha Omega. Alpha Publishing, Cardiff, 1972, p 189Google Scholar
  3. 3.
    Bradley CJ, Kledzik GS, Meites J: Prolactin and estrogen dependency of rat mammary cancers at early and late stages of development. Cancer Res 36:319–324, 1976PubMedGoogle Scholar
  4. 4.
    Manni A, Trujillo JE, Pearson OH: Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz (a) anthracene-induced rat mammary tumor. Cancer Res 37:1216–1219, 1977Google Scholar
  5. 5.
    Lippman ME, Bolan G, Huff K: The effects of glucocorticoïds and progesterone on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36: 4602–4609, 1976Google Scholar
  6. 6.
    Osborne CK, Monaco ME, Kahr CR, Huff K, Bronzert D, Lippman ME: Direct inhibition of growth and antagonism of insulin action by glucocorticoids in human breast cancer cells in culture. Cancer Res 39:2422–2428, 1979Google Scholar
  7. 7.
    Huggins C, Moon RC, Morii S: Extinction of experimental mammary cancer. I. Estradiol-17ß and progesterone. Proc Natl Acad Sci USA, 48:379–386, 1962PubMedGoogle Scholar
  8. 8.
    Stoll BA: Progestin therapy of breast cancer: Comparison of agents. Brit J Med 1:338, 1967Google Scholar
  9. 9.
    Clark JH, Klee W, Levitzki A, Wolff J (eds): Hormone and antihormone action at the target cell. Dahlem Konferenzen, Life Science Research, Report 3, 1976Google Scholar
  10. 10.
    Samuels HH, Tomkins GM: Relation of steroid structure to enzyme induction in hepatoma tissue culture cells. J Mol Biol 52:57–74, 1970PubMedGoogle Scholar
  11. 11.
    Bullock LP, Bardin WC, Sherman MR: Androgenic, antiandrogenic and synandrogenic actions of progestins: Role of steric and allosteric interactions with androgen receptors. Endocrinology 103:1768–1782, 1978PubMedGoogle Scholar
  12. 12.
    Westley B, Rochefort H: A secreted glycoprotein induced by estrogen in human breast cancer cell lines. Cell 20:353–362, 1980PubMedGoogle Scholar
  13. 13.
    Edwards DP, Adams DJ, Savage N, McGuire WL: Estrogen induced synthesis of specific proteins in human breast cancer cells. Biochem Biophys Res Commun 93: 804, 1980PubMedGoogle Scholar
  14. 14.
    Lippman M, Bolan G, Huff K: The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4595–4601, 1976Google Scholar
  15. 15.
    Shafie SM: Estrogen and the growth of breast cancer: New evidence suggests indirect action. Science 209:701–702, 1980PubMedGoogle Scholar
  16. 16.
    Cohen LA, Tsuang J, Chan PC: Characteristics of rat normal mammary epithelial cells and dimethylbenz (a) anthracene induced mammary adenocarcinoma cells grown in monolayer culture. In Vitro 10:51–62, 1974PubMedGoogle Scholar
  17. 17.
    Chan PC, Head J, Tsuang J: Growth response of two rat mammary tumor cell lines to hormone. In Vitro 13:190, 1977 (abstract 189)Google Scholar
  18. 18.
    Rochefort H, Coezy E, Joly E, Westley B, Vignon F: Hormonal control of breast cancer in cell culture.In S Iacobelli, RJB King, HR Lindner, ME Lippman (eds): Hormones and Cancer, Progress in Cancer Research and Therapy, vol 14. Raven Press, New York, 1980, pp 21–30Google Scholar
  19. 19.
    King RJB, Cambray GJ, Jagus-Smith R, Robinson JH, Smith JA: Steroid hormones and the control of tumor growth: Studies on androgen-responsive tumor cells in culture.In JR Pasqualini (ed): Receptors and Mechanism of Action of Steroid Hormones, part I, 1977, pp 215–260Google Scholar
  20. 20.
    Gullino PM, Pettigrew HM, Grantham FH: N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst 54:401–414, 1975PubMedGoogle Scholar
  21. 21.
    Brooks RF: Continuous protein synthesis is required to maintain the probability of entry into S phase. Cell 12: 311, 1977PubMedGoogle Scholar
  22. 22.
    Kissane JM, Robins E: The fluorimetric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem 233: 184–193, 1958PubMedGoogle Scholar
  23. 23.
    Chan PC, Head JF, Rochefort H: Growth response of two rat mammary tumor cell lines to hormones, 11th Meeting on Mammary Cancer in Experimental Animals and Man. Detroit, June 1978 (Abstract 110)Google Scholar
  24. 24.
    Lippman ME, Aitken SC: Estrogen and anti-estrogen effects on thymidine utilization by MCF-human breast cancer cells in tissue culture.In S Iacobelli, RJB King, HR Lindner, ME Lippman (eds): Hormones and Cancer, Progress in Cancer Research and Therapy, vol 14. Raven Press, New York, 1980, pp 1–20Google Scholar
  25. 25.
    Raynaud JP: R5020, a tag for the progestin receptor.In WL McGuire, JP Raynaud and EE Baulieu (eds): Progesterone receptors in normal and neoplastic tissues. Raven Press, New York, 1977, p 9Google Scholar
  26. 26.
    Pasteels JL, Heuson JC, Heuson-Stiennon J, Legros N: Effects of insulin, prolactin, progesterone and estradiol on DNA synthesis in organ culture of 7, 12-dimethylbenz (a) anthracene-induced rat mammary tumors. Cancer Res 36:2162–2170, 1976PubMedGoogle Scholar
  27. 27.
    Devinoy E, Houdebine LM: Effects of glucocorticoids on casein gene expression in the rabbit. Eur J Biochem 75:411–416, 1977PubMedGoogle Scholar
  28. 28.
    Juergens WG, Stockdale FE, Topper YJ, Elias JJ: Hormone-dependent differentiation of mammary glandin vitro. Proc Natl Acad Sci USA, 54:629–634, 1965PubMedGoogle Scholar
  29. 29.
    Hallowes RC, Rudland PS, Hawkins RA, Lewis DJ, Bennett D, Durbin H: Comparison of the effects of hormones on DNA synthesis in cell cultures of nonneoplastic and neoplastic mammary epithelium from rat. Cancer Res 37:2492–2504, 1977Google Scholar
  30. 30.
    Gillette RW, Wunderlich DA: Accelerated growth of mammary tumor cells in normal and athymic mice after treatment in vitro with dexamethasone. Cancer Res 38: 3146–3149, 1978PubMedGoogle Scholar
  31. 31.
    Cohen SS: Meeting Report. Conference on polyamines in cancer. Cancer Res 37:939–942, 1977Google Scholar
  32. 32.
    Russel DH, McVicker TA: Polyamines biogenesis in the rat mammary gland during pregnancy and lactation. Biochem J 130:71–76, 1972PubMedGoogle Scholar
  33. 33.
    Oka T, Perry JW: Spermidine as a possible mediator of glucocorticoid effect on milk protein synthesis in mouse mammary epithelium in vitro. J Biol Chem 249:7647–7652, 1974PubMedGoogle Scholar
  34. 34.
    Baker JB, Simmer RL, Glenn KC, Cunningham DD: Glucocorticoids enhance the mitogenic action of insulin in serum-free cultures of chick embryo cells. J Cell Physiol 98:561–570, 1979PubMedGoogle Scholar
  35. 35.
    Baker JB, Barsh GS, Carney DH, Cunningham DD: Dexamethasone modulates binding and action of epidermal growth factor in serum free cell culture. Proc Natl Acad Sci USA 75:1882–1886, 1978PubMedGoogle Scholar
  36. 36.
    Garcia M, Rochefort H: Androgen effects mediated by estrogen receptor in 7, 12-dimethylbenz (a) anthraceneinduced rat mammary tumors. Cancer Res 38:3922–3929, 1978Google Scholar
  37. 37.
    Huggins C, Briziarelli G, Sutton H Jr: Rapid induction of mammary carcinoma in the rat and the influence of hormones on the tumors. J Exptl Med 109:25–41, 1959Google Scholar
  38. 38.
    Thompson EB, Lippman ME: Mechanism of action of glucocorticoids. Metab Clin Exptl 23:159–202, 1974Google Scholar
  39. 39.
    Mauvais-Jarvis P, Kuttenn F, Mowszowicz I, Sitruk-Ware R: Mastopathies bénignes: Etude hormonale chez 125 malades. La Nouvelle Presse Médicale 44:4115–4118, 1977Google Scholar
  40. 40.
    McGuire WL, Horwitz KB, Chamness GC, Zava DT: A physiological role for estrogen and progesterone in breast cancer. J Steroid Biochem 7:875–882, 1976PubMedGoogle Scholar

Copyright information

© Martinus Nijhoff Publishers 1982

Authors and Affiliations

  • E. Joly
    • 1
  • F. Vignon
    • 1
  • H. Rochefort
    • 1
  1. 1.INSERMMontpellierFrance

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