Abstract
A cDNA library was constructed from the mRNA of the ZR-75 oestrogen responsive human breast cancer cell line and screened for oestrogen regulated mRNA sequences. Of the recombinants isolated, 30 contained cDNA that corresponded to a single mRNA species of 2.1 kb that was induced between 10 and 15 fold by oestradiol treatment. The sequence of the entire open reading frame and 3' non-coding region of the mRNA was determined and shown to encode the aspartyl protease cathepsin D. The induction of cathepsin D mRNA is specific for oestrogen and is maximal at 3 X 10(-10) M. Cathepsin D mRNA levels were increased by oestrogen in 3 oestrogen responsive breast cancer cell lines. Cathepsin D mRNA was expressed but not regulated in an oestrogen receptor negative breast tumour cell line, BT 20, and in 2 other malignant cell lines, Hela and A431.
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Selected References
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- 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]
- Capony F., Garcia M., Capdevielle J., Rougeot C., Ferrara P., Rochefort H. Purification and first characterization of the secreted and cellular 52-kDa proteins regulated by estrogens in human-breast cancer cells. Eur J Biochem. 1986 Dec 1;161(2):505–512. doi: 10.1111/j.1432-1033.1986.tb10471.x. [DOI] [PubMed] [Google Scholar]
- Chalbos D., Vignon F., Keydar I., Rochefort H. Estrogens stimulate cell proliferation and induce secretory proteins in a human breast cancer cell line (T47D). J Clin Endocrinol Metab. 1982 Aug;55(2):276–283. doi: 10.1210/jcem-55-2-276. [DOI] [PubMed] [Google Scholar]
- 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]
- Edwards D. P., Adams D. J., Savage N., McGuire W. L. Estrogen induced synthesis of specific proteins in human breast cancer cells. Biochem Biophys Res Commun. 1980 Apr 14;93(3):804–812. doi: 10.1016/0006-291x(80)91148-1. [DOI] [PubMed] [Google Scholar]
- Elangovan S., Moulton B. C. Progesterone and estrogen control of rates of synthesis of uterine cathepsin D. J Biol Chem. 1980 Aug 10;255(15):7474–7479. [PubMed] [Google Scholar]
- Engel L. W., Young N. A., Tralka T. S., Lippman M. E., O'Brien S. J., Joyce M. J. Establishment and characterization of three new continuous cell lines derived from human breast carcinomas. Cancer Res. 1978 Oct;38(10):3352–3364. [PubMed] [Google Scholar]
- Fabricant R. N., De Larco J. E., Todaro G. J. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. doi: 10.1073/pnas.74.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gal S., Gottesman M. M. The major excreted protein of transformed fibroblasts is an activable acid-protease. J Biol Chem. 1986 Feb 5;261(4):1760–1765. [PubMed] [Google Scholar]
- Garcia M., Salazar-Retana G., Pages A., Richer G., Domergue J., Pages A. M., Cavalie G., Martin J. M., Lamarque J. L., Pau B. Distribution of the Mr 52,000 estrogen-regulated protein in benign breast diseases and other tissues by immunohistochemistry. Cancer Res. 1986 Jul;46(7):3734–3738. [PubMed] [Google Scholar]
- Goldberg D. A. Isolation and partial characterization of the Drosophila alcohol dehydrogenase gene. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5794–5798. doi: 10.1073/pnas.77.10.5794. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horwitz K. B., Koseki Y., McGuire W. L. Estrogen control of progesterone receptor in human breast cancer: role of estradiol and antiestrogen. Endocrinology. 1978 Nov;103(5):1742–1751. doi: 10.1210/endo-103-5-1742. [DOI] [PubMed] [Google Scholar]
- Jakowlew S. B., Breathnach R., Jeltsch J. M., Masiakowski P., Chambon P. Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7. Nucleic Acids Res. 1984 Mar 26;12(6):2861–2878. doi: 10.1093/nar/12.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keydar I., Chen L., Karby S., Weiss F. R., Delarea J., Radu M., Chaitcik S., Brenner H. J. Establishment and characterization of a cell line of human breast carcinoma origin. Eur J Cancer. 1979 May;15(5):659–670. doi: 10.1016/0014-2964(79)90139-7. [DOI] [PubMed] [Google Scholar]
- LASFARGUES E. Y., OZZELLO L. Cultivation of human breast carcinomas. J Natl Cancer Inst. 1958 Dec;21(6):1131–1147. [PubMed] [Google Scholar]
- Lippman M. E., Bolan G. Oestrogen-responsive human breast cancer in long term tissue culture. Nature. 1975 Aug 14;256(5518):592–593. doi: 10.1038/256592a0. [DOI] [PubMed] [Google Scholar]
- 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]
- May F. E., Westley B. R. Cloning of estrogen-regulated messenger RNA sequences from human breast cancer cells. Cancer Res. 1986 Dec;46(12 Pt 1):6034–6040. [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Morrison R. I., Barrett A. J., Dingle J. T., Prior D. Cathepsins BI and D. Action on human cartilage proteoglycans. Biochim Biophys Acta. 1973 Apr 12;302(2):411–419. doi: 10.1016/0005-2744(73)90170-8. [DOI] [PubMed] [Google Scholar]
- Osborne C. K., Yochmowitz M. G., Knight W. A., 3rd, McGuire W. L. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer. 1980 Dec 15;46(12 Suppl):2884–2888. doi: 10.1002/1097-0142(19801215)46:12+<2884::aid-cncr2820461429>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
- Queen C., Korn L. J. A comprehensive sequence analysis program for the IBM personal computer. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 2):581–599. doi: 10.1093/nar/12.1part2.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Recklies A. D., Tiltman K. J., Stoker T. A., Poole A. R. Secretion of proteinases from malignant and nonmalignant human breast tissue. Cancer Res. 1980 Mar;40(3):550–556. [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Shewale J. G., Tang J. Amino acid sequence of porcine spleen cathepsin D. Proc Natl Acad Sci U S A. 1984 Jun;81(12):3703–3707. doi: 10.1073/pnas.81.12.3703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sloane B. F., Honn K. V., Sadler J. G., Turner W. A., Kimpson J. J., Taylor J. D. Cathepsin B activity in B16 melanoma cells: a possible marker for metastatic potential. Cancer Res. 1982 Mar;42(3):980–986. [PubMed] [Google Scholar]
- 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]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Tang J. Evolution in the structure and function of carboxyl proteases. Mol Cell Biochem. 1979 Jul 31;26(2):93–109. doi: 10.1007/BF00232887. [DOI] [PubMed] [Google Scholar]
- Terayama H., Morioka M., Koji T. Mitogenic effects of certain cathepsins and calciferin on the intact liver in vivo. Int J Biochem. 1985;17(9):949–955. doi: 10.1016/0020-711x(85)90239-3. [DOI] [PubMed] [Google Scholar]
- 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]
- Westley B., May F. E. The human genome contains multiple sequences of varying homology to mouse mammary tumour virus DNA. Gene. 1984 May;28(2):221–227. doi: 10.1016/0378-1119(84)90259-2. [DOI] [PubMed] [Google Scholar]
- 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]