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Katzenellenbogen, Benita S. Read, Linnea Diane 2011-05-07T14:17:53Z 2011-05-07T14:17:53Z 10000-01-01 1990 Since sex steroids modulate breast tumor growth, and high levels of the HER-2/neu protooncogene protein may contribute to breast cancer metastasis, the effects of estrogen, progestin and hormone antagonists on the levels of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu mRNA and protein have been studied in human breast cancer cell lines using cDNA and antibody probes. In all studies, protein response closely followed the RNA response. In MCF-7 cells, which contain high levels of ER and an estradiol (E$\sb2$) induced PR, 1 nM E$\sb2$ caused a 60% drop in ER mRNA (6.6 kb), a 10-fold rise in PR mRNA (5 species: 11.4, 5.8, 5.3, 3.5, 2.8 kb), and a 60% drop in HER-2neu mRNA levels (4.8 kb). These effects were dose-dependent (maximal effects $\geq$ 10$\sp{-10}$M), and were blocked by addition of excess antiestrogen. Treatment with the progestin R5020 (10 nM) partly reversed E$\sb2$ effects on ER. R5020 and the antiprogestin RU486 (10 nM) both reduced PR mRNA levels by 50% but did not change HER-2/neu. In T47D cells, which contain low ER and high PR levels, E$\sb2$ induced ER mRNA 2.5-fold in 2d. In contrast, R5020 reduced both ER mRNA and PR mRNA levels to 20% of control in 2d. RU486 caused an initial 50% drop by 6h followed by a rise to control levels by 48h. In T47D, no hormone studied changed HER-2/neu levels. Conclusions: (1) sex steroid hormones regulate their own receptors at the mRNA and protein levels, (2) progestin antagonizes E$\sb2$ effects, (3) these E$\sb2$ effects are mediated via ER (based on dose-dependence and antiestrogen antagonism), and (4) aggressiveness related to E$\sb2$-treatment in MCF-7 cells is not associated with increased levels of HER-2/neu. Made available in DSpace on 2011-05-07T14:17:53Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9114379.pdf: 4379295 bytes, checksum: b354e53aab50c1bbaa20147a1db6b004 (MD5) Previous issue date: 1990 Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T15:05:09Z Item is restricted indefinitely. Restriction data tranferred 2014-07-01T11:31:11-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission ETDs are only available to UIUC Users without author permission U of I Only AAI9114379 (UMI)AAI9114379 http://hdl.handle.net/2142/23537 eng Copyright 1990 Read, Linnea Diane Biology, Molecular Biology, Animal Physiology Hormonal modulation of sex steroid hormone receptors and oncogenes in human breast cancer cells text Biology, Molecular Biology, Animal Physiology Biology, Molecular Biology, Animal Physiology University of Illinois at Urbana-Champaign Dissertation Ph.D.