The estrogen receptor mediates the stimulatory effect of estradiol/progestin combinations in breast cancer cells overexpressing the progesterone receptor membrane component-1
Prof. Harald Seeger
Germany 
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6 slide(s) – English – 2012-03-28
The estrogen receptor mediates the stimulatory effect of estradiol/progestin combinations in breast cancer cells overexpressing the progesterone receptor membrane component-1
Jing Zhou1, Helen Schneck2, Hans Neubauer2, Harald Seeger2, Tanja Fehm2, Michael A Cahill3, Qi Yu1, Alfred O Mueck2
1 Dept. of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China
2 University Women’s Hospital, Tübingen, Germany
3 School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia
Objectives: Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. We investigated the influence of estradiol and progestin addition on breast cancer cells overexpressing PGRMC1.
Methods: MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12 cells). To test the effects of the steroids on proliferation the cells were stimulated with different concentrations of estradiol (E, 10-10 M and 10-12 M) alone and in combination with norethisterone (EP) (10-7 M). To evaluate the mechanism(s) receptor antagonists for estrogen receptor-alpha (ER), progesterone receptor (PR) and PGRMC1 were used alone and in combination with E and EP.
Results: Estradiol elicited a concentration-dependent proliferative effect on WT-12 cells of about 200% at 10-10 M. The EP combination showed a similar increase, but at both E concentrations. In blocking experiments with antagonists of ER (fulvestrant), PR (RU 486) or PGRMC1 (AG 205) only the presence of fulvestrant was able to totally block the E and EP induced proliferation. Partial significant effects could be found in the presence of AG 205, no effect was observed for RU 486.
Conclusion: Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol and estradiol/norethisterone combination. This effect appears to be mediated mainly by the estrogen receptor-alpha. Breast cancer tumorigenesis may depend on the concentration of estrogen as well as the specific progestogen used.
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