Apoptosis and proliferation in breast cancer cells, cultured in vitro: effects of SERMs.
OBJECTIVE
Selective estrogen receptor modulators (SERMs) decrease the risk of developing breast cancer. As an antagonistic effect, SERMs may aggravate or induce climacteric symptoms. Hormone therapy (HT) would be able to alleviate these symptoms. The present in vitro study tries to elucidate the effects of several HT preparations combined with SERMs on estrogen receptor-positive (ER +) (i.e. MCF-7 and T-47D) and -negative (ER-) (i.e. MDA-MB-231) human breast cancer cells in vitro.


METHODS
We performed experiments with various HT preparations (estradiol (E2)/E2 + progesterone/E2 + dihydrodydrogesterone /E2 + norethisterone acetate/E2 + medroxyprogesterone acetate/tibolone) in the concentration of 10(-6) mol/l together with SERMs (raloxifene or tamoxifen) added to different breast cancer cell lines in vitro. After an incubation period of 144 h, proliferation and apoptosis were measured. The first was measured by quantification of the expression of cyclin D1 mRNA, the latter by the Nicoletti method.


RESULTS
This in vitro study clearly demonstrates differences in results if various HT preparations, combined with SERMs, are added to ER + and ER- breast cancer cell lines.


CONCLUSIONS
Adding estradiol/progestogens in combination with a SERM to estrogen receptor-positive breast cancer cell lines does not obligatorily lead to proliferation of tumor cells. Not all progestogens act equally.
Werner
H M J
HM
Departments of Obstetrics and Gynecology, Medisch Spectrum Twente Hospital Group, Enschede, The Netherlands.
Franke
H R
HR
Vermes
I
I
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004394:Dydrogesterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D009640:Norethindrone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003271:Contraceptive Agents, Female; D009652:Norpregnenes; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D011374:Progesterone; D004958:Estradiol; D004394:Dydrogesterone; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; C027385:tibolone; D009640:Norethindrone