Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Apr;61(4):504–507. doi: 10.1038/bjc.1990.114

High progesterone receptor concentration in a variant of the ZR-75-1 human breast cancer cell line adapted to growth in oestrogen free conditions.

H W van den Berg 1, J Martin 1, M Lynch 1
PMCID: PMC1971370  PMID: 2139575

Abstract

Culture of ZR-75-1 human breast cancer cells for 5 days in the absence of oestrogens (phenol red-free medium supplemented with dextran coated charcoal stripped 5% fetal calf serum) resulted in a slowing of growth rate and loss of progesterone receptors. Oestradiol at 10(-9) M markedly stimulated growth and progesterone receptor synthesis over a 5-day period. While medroxyprogesterone acetate (10(-10) to 10(-6) M) inhibited growth of ZR-75-1 cells growing in complete medium, in the short-term absence of oestrogens low concentrations were growth stimulatory. Cells deprived of oestrogens for 5 days retained sensitivity to growth inhibition by 4-hydroxy tamoxifen. ZR-75-1 cells were also adapted to growth in the absence of oestrogens over a 5-month period. These cells (ZR-PR-LT) failed to express binding sites characteristic of the type 1 oestrogen receptor but progesterone receptor expression was at a level normally associated with oestrogen induction. Adapted cells were growth inhibited by oestradiol, 4-hydroxy tamoxifen and medroxyprogesterone acetate, but despite elevated progesterone receptor expression the progestin was only marginally more inhibitory than in the parent line. Our data indicate a poor quantitative relationship between response to progestins in vitro and progesterone receptor concentration and support previous findings that acquisition of an oestrogen independent phenotype does not necessarily result in resistance to anti-oestrogens.

Full text

PDF
506

Selected References

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

  1. Berthois Y., Katzenellenbogen J. A., Katzenellenbogen B. S. Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2496–2500. doi: 10.1073/pnas.83.8.2496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braunsberg H., Coldham N. G., Leake R. E., Cowan S. K., Wong W. Actions of a progestogen on human breast cancer cells: mechanisms of growth stimulation and inhibition. Eur J Cancer Clin Oncol. 1987 May;23(5):563–571. doi: 10.1016/0277-5379(87)90321-x. [DOI] [PubMed] [Google Scholar]
  3. Bronzert D. A., Greene G. L., Lippman M. E. Selection and characterization of a breast cancer cell line resistant to the antiestrogen LY 117018. Endocrinology. 1985 Oct;117(4):1409–1417. doi: 10.1210/endo-117-4-1409. [DOI] [PubMed] [Google Scholar]
  4. Clark G. M., McGuire W. L. Progesterone receptors and human breast cancer. Breast Cancer Res Treat. 1983;3(2):157–163. doi: 10.1007/BF01803558. [DOI] [PubMed] [Google Scholar]
  5. Darbre P. D., King R. J. Role of receptor occupancy in the transition from responsive to unresponsive states in cultured breast tumor cells. J Cell Biochem. 1988 Jan;36(1):83–89. doi: 10.1002/jcb.240360109. [DOI] [PubMed] [Google Scholar]
  6. Glover J. F., Irwin J. T., Darbre P. D. Interaction of phenol red with estrogenic and antiestrogenic action on growth of human breast cancer cells ZR-75-1 and T-47-D. Cancer Res. 1988 Jul 1;48(13):3693–3697. [PubMed] [Google Scholar]
  7. Hansen J. C., Gorski J. Conformational transitions of the estrogen receptor monomer. Effects of estrogens, antiestrogen, and temperature. J Biol Chem. 1986 Oct 25;261(30):13990–13996. [PubMed] [Google Scholar]
  8. Hissom J. R., Moore M. R. Progestin effects on growth in the human breast cancer cell line T-47D--possible therapeutic implications. Biochem Biophys Res Commun. 1987 Jun 15;145(2):706–711. doi: 10.1016/0006-291x(87)91022-9. [DOI] [PubMed] [Google Scholar]
  9. Horwitz K. B., Mockus M. B., Lessey B. A. Variant T47D human breast cancer cells with high progesterone-receptor levels despite estrogen and antiestrogen resistance. Cell. 1982 Mar;28(3):633–642. doi: 10.1016/0092-8674(82)90218-5. [DOI] [PubMed] [Google Scholar]
  10. Humphries J. E., Isaacs J. T. Unusual androgen sensitivity of the androgen-independent Dunning R-3327-G rat prostatic adenocarcinoma: androgen effect on tumor cell loss. Cancer Res. 1982 Aug;42(8):3148–3156. [PubMed] [Google Scholar]
  11. Katzenellenbogen B. S., Kendra K. L., Norman M. J., Berthois Y. Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. Cancer Res. 1987 Aug 15;47(16):4355–4360. [PubMed] [Google Scholar]
  12. Manni A., Badger B., Wright C., Ahmed S. R., Demers L. M. Effects of progestins on growth of experimental breast cancer in culture: interaction with estradiol and prolactin and involvement of the polyamine pathway. Cancer Res. 1987 Jun 15;47(12):3066–3071. [PubMed] [Google Scholar]
  13. Martin P. M., Berthois Y., Jensen E. V. Binding of antiestrogens exposes an occult antigenic determinant in the human estrogen receptor. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2533–2537. doi: 10.1073/pnas.85.8.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nardulli A. M., Katzenellenbogen B. S. Progesterone receptor regulation in T47D human breast cancer cells: analysis by density labeling of progesterone receptor synthesis and degradation and their modulation by progestin. Endocrinology. 1988 Apr;122(4):1532–1540. doi: 10.1210/endo-122-4-1532. [DOI] [PubMed] [Google Scholar]
  15. Nawata H., Bronzert D., Lippman M. E. Isolation and characterization of a tamoxifen-resistant cell line derived from MCF-7 human breast cancer cells. J Biol Chem. 1981 May 25;256(10):5016–5021. [PubMed] [Google Scholar]
  16. Panko W. B., Watson C. S., Clark J. H. The presence of a second, specific estrogen binding site in human breast cancer. J Steroid Biochem. 1981 Dec;14(12):1311–1316. doi: 10.1016/0022-4731(81)90337-x. [DOI] [PubMed] [Google Scholar]
  17. Reddel R. R., Alexander I. E., Koga M., Shine J., Sutherland R. L. Genetic instability and the development of steroid hormone insensitivity in cultured T 47D human breast cancer cells. Cancer Res. 1988 Aug 1;48(15):4340–4347. [PubMed] [Google Scholar]
  18. Schneider M. R., Michna H., Nishino Y., el Etreby M. F. Antitumor activity of the progesterone antagonists ZK 98.299 and RU 38.486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA- and the MNU-induced mammary tumor models of the rat. Eur J Cancer Clin Oncol. 1989 Apr;25(4):691–701. doi: 10.1016/0277-5379(89)90206-x. [DOI] [PubMed] [Google Scholar]
  19. Sluyser M., Van Nie R. Estrogen receptor content and hormone-responsive growth of mouse mammary tumors. Cancer Res. 1974 Dec;34(12):3253–3257. [PubMed] [Google Scholar]
  20. Welshons W. V., Jordan V. C. Adaptation of estrogen-dependent MCF-7 cells to low estrogen (phenol red-free) culture. Eur J Cancer Clin Oncol. 1987 Dec;23(12):1935–1939. doi: 10.1016/0277-5379(87)90062-9. [DOI] [PubMed] [Google Scholar]
  21. van den Berg H. W., Leahey W. J., Lynch M., Clarke R., Nelson J. Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen. Br J Cancer. 1987 Mar;55(3):255–257. doi: 10.1038/bjc.1987.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. van den Berg H. W., Lynch M., Martin J., Nelson J., Dickson G. R., Crockard A. D. Characterisation of a tamoxifen-resistant variant of the ZR-75-1 human breast cancer cell line (ZR-75-9a1) and ability of the resistant phenotype. Br J Cancer. 1989 Apr;59(4):522–526. doi: 10.1038/bjc.1989.107. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES