Hormonal modulation of sex steroid hormone receptors and oncogenes in human breast cancer cells
Read, Linnea Diane
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Permalink
https://hdl.handle.net/2142/23537
Description
Title
Hormonal modulation of sex steroid hormone receptors and oncogenes in human breast cancer cells
Author(s)
Read, Linnea Diane
Issue Date
1990
Doctoral Committee Chair(s)
Katzenellenbogen, Benita S.
Department of Study
Biology, Molecular
Biology, Animal Physiology
Discipline
Biology, Molecular
Biology, Animal Physiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Molecular
Biology, Animal Physiology
Language
eng
Abstract
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.
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