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. 1988 Mar 25;16(5 Pt B):1903–1919. doi: 10.1093/nar/16.5.1903

Estrogens and growth factors induce the mRNA of the 52K-pro-cathepsin-D secreted by breast cancer cells.

V Cavailles 1, P Augereau 1, M Garcia 1, H Rochefort 1
PMCID: PMC338189  PMID: 3282224

Abstract

The estrogen-induced 52K protein secreted by human breast cancer cells is a lysosomal protease recently identified as a pro-cathepsin D by sequencing several cDNA clones isolated from MCF7 cells (Augereau et al., Mol. Endocr.). Using one of these clones, we detected, in MCF7 cells, a 2.2 kb mRNA whose level was rapidly increased 4- to 10-fold by estradiol, but not by other classes of steroids. Other mitogens, such as epidermal growth factor and insulin, also induced the 2.2 kb mRNA in a dose-dependent manner. Induction with epidermal growth factor was as rapid but was 2- to 3-fold lower than with estradiol. Antiestrogens had no effect on the 52K-cathepsin-D mRNA in MCF7 cells, but became estrogen agonists in two antiestrogen-resistant sublines R27 and LY2. The use of transcription and translation inhibitors and nuclear run-on experiments indicate that estradiol enhances transcription of the 52K-cathepsin-D gene in MCF7 cells.

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Selected References

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

  1. Adams D. J., Edwards D. P., McGuire W. L. Estrogen regulation of specific messinger RNA's in human breast cancer cells. Biochem Biophys Res Commun. 1980 Dec 31;97(4):1354–1361. doi: 10.1016/s0006-291x(80)80016-7. [DOI] [PubMed] [Google Scholar]
  2. Aitken S. C., Lippman M. E., Kasid A., Schoenberg D. R. Relationship between the expression of estrogen-regulated genes and estrogen-stimulated proliferation of MCF-7 mammary tumor cells. Cancer Res. 1985 Jun;45(6):2608–2615. [PubMed] [Google Scholar]
  3. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Brown A. M., Jeltsch J. M., Roberts M., Chambon P. Activation of pS2 gene transcription is a primary response to estrogen in the human breast cancer cell line MCF-7. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6344–6348. doi: 10.1073/pnas.81.20.6344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Capony F., Morisset M., Barrett A. J., Capony J. P., Broquet P., Vignon F., Chambon M., Louisot P., Rochefort H. Phosphorylation, glycosylation, and proteolytic activity of the 52-kD estrogen-induced protein secreted by MCF7 cells. J Cell Biol. 1987 Feb;104(2):253–262. doi: 10.1083/jcb.104.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chalbos D., Westley B., May F., Alibert C., Rochefort H. Cloning of cDNA sequences of a progestin-regulated mRNA from MCF7 human breast cancer cells. Nucleic Acids Res. 1986 Jan 24;14(2):965–982. doi: 10.1093/nar/14.2.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davidson N. E., Bronzert D. A., Chambon P., Gelmann E. P., Lippman M. E. Use of two MCF-7 cell variants to evaluate the growth regulatory potential of estrogen-induced products. Cancer Res. 1986 Apr;46(4 Pt 2):1904–1908. [PubMed] [Google Scholar]
  9. Faust P. L., Kornfeld S., Chirgwin J. M. Cloning and sequence analysis of cDNA for human cathepsin D. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4910–4914. doi: 10.1073/pnas.82.15.4910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feinberg A. P., Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. doi: 10.1016/0003-2697(84)90381-6. [DOI] [PubMed] [Google Scholar]
  11. Garcia M., Capony F., Derocq D., Simon D., Pau B., Rochefort H. Characterization of monoclonal antibodies to the estrogen-regulated Mr 52,000 glycoprotein and their use in MCF7 cells. Cancer Res. 1985 Feb;45(2):709–716. [PubMed] [Google Scholar]
  12. Garcia M., Lacombe M. J., Duplay H., Cavailles V., Derocq D., Delarue J. C., Krebs B., Contesso G., Sancho-Garnier H., Richer G. Immunohistochemical distribution of the 52-kDa protein in mammary tumors: a marker associated with cell proliferation rather than with hormone responsiveness. J Steroid Biochem. 1987;27(1-3):439–445. doi: 10.1016/0022-4731(87)90338-4. [DOI] [PubMed] [Google Scholar]
  13. Lippman M. E., Dickson R. B., Bates S., Knabbe C., Huff K., Swain S., McManaway M., Bronzert D., Kasid A., Gelmann E. P. 8th San Antonio Breast Cancer Symposium--Plenary lecture. Autocrine and paracrine growth regulation of human breast cancer. Breast Cancer Res Treat. 1986;7(2):59–70. doi: 10.1007/BF01806790. [DOI] [PubMed] [Google Scholar]
  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. 1976 Dec;36(12):4595–4601. [PubMed] [Google Scholar]
  15. Masiakowski P., Breathnach R., Bloch J., Gannon F., Krust A., Chambon P. Cloning of cDNA sequences of hormone-regulated genes from the MCF-7 human breast cancer cell line. Nucleic Acids Res. 1982 Dec 20;10(24):7895–7903. doi: 10.1093/nar/10.24.7895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morisset M., Capony F., Rochefort H. Processing and estrogen regulation of the 52-kilodalton protein inside MCF7 breast cancer cells. Endocrinology. 1986 Dec;119(6):2773–2782. doi: 10.1210/endo-119-6-2773. [DOI] [PubMed] [Google Scholar]
  17. Morisset M., Capony F., Rochefort H. The 52-kDa estrogen-induced protein secreted by MCF7 cells is a lysosomal acidic protease. Biochem Biophys Res Commun. 1986 Jul 16;138(1):102–109. doi: 10.1016/0006-291x(86)90252-4. [DOI] [PubMed] [Google Scholar]
  18. Moulton B. C., Koenig B. B. Progestin increases cathepsin D synthesis in uterine luminal epithelial cells. Am J Physiol. 1983 May;244(5):E442–E446. doi: 10.1152/ajpendo.1983.244.5.E442. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Osborne C. K., Bolan G., Monaco M. E., Lippman M. E. Hormone responsive human breast cancer in long-term tissue culture: effect of insulin. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4536–4540. doi: 10.1073/pnas.73.12.4536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rabin M. S., Doherty P. J., Gottesman M. M. The tumor promoter phorbol 12-myristate 13-acetate induces a program of altered gene expression similar to that induced by platelet-derived growth factor and transforming oncogenes. Proc Natl Acad Sci U S A. 1986 Jan;83(2):357–360. doi: 10.1073/pnas.83.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rochefort H., Capony F., Garcia M., Cavaillès V., Freiss G., Chambon M., Morisset M., Vignon F. Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? J Cell Biochem. 1987 Sep;35(1):17–29. doi: 10.1002/jcb.240350103. [DOI] [PubMed] [Google Scholar]
  23. Soule H. D., Vazguez J., Long A., Albert S., Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst. 1973 Nov;51(5):1409–1416. doi: 10.1093/jnci/51.5.1409. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Vignon F., Capony F., Chambon M., Freiss G., Garcia M., Rochefort H. Autocrine growth stimulation of the MCF 7 breast cancer cells by the estrogen-regulated 52 K protein. Endocrinology. 1986 Apr;118(4):1537–1545. doi: 10.1210/endo-118-4-1537. [DOI] [PubMed] [Google Scholar]
  26. Vignon F., Lippman M. E., Nawata H., Derocq D., Rochefort H. Induction of two estrogen-responsive proteins by antiestrogens in R27, a tamoxifen-resistant clone of MCF7 cells. Cancer Res. 1984 May;44(5):2084–2088. [PubMed] [Google Scholar]
  27. Westley B. R., May F. E. Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human breast cancer cells. Nucleic Acids Res. 1987 May 11;15(9):3773–3786. doi: 10.1093/nar/15.9.3773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Westley B., May F. E., Brown A. M., Krust A., Chambon P., Lippman M. E., Rochefort H. Effects of antiestrogens on the estrogen-regulated pS2 RNA and the 52- and 160-kilodalton proteins in MCF7 cells and two tamoxifen-resistant sublines. J Biol Chem. 1984 Aug 25;259(16):10030–10035. [PubMed] [Google Scholar]
  29. Westley B., Rochefort H. A secreted glycoprotein induced by estrogen in human breast cancer cell lines. Cell. 1980 Jun;20(2):353–362. doi: 10.1016/0092-8674(80)90621-2. [DOI] [PubMed] [Google Scholar]

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