Sensitization of MCF-7 breast cancer cells to the apoptotic effect of estradiol.
A new substrain of hormone-resistant MCF-7/T breast cancer cells was selected after long-term culturing of estrogen-dependent MCF-7 cells in the presence of tamoxifen. These cells were resistant to the growth-stimulating and cytostatic effects of estradiol and tamoxifen, respectively. MCF-7/T cells gained paradoxical sensitivity to the apoptotic effect of estradiol. Estradiol stimulated p53 expression and decreased DNA-binding activity of NF-kappaB. Our findings provide indirect evidence that these proteins are involved in the regulation of estrogen-induced apoptosis. These results indicate that tamoxifen-resistant breast cancer cells can be sensitized to the apoptotic effect of estradiol. The data form a basis for the development of new methods of endocrine therapy for breast cancer patients.
Shcherbakov
A M
AM
N. N. Blokhin Russian Cancer Research Center, Moscow. cesaro@front.ru
Lobanova
Yu S
YS
Shatskaya
V A
VA
Onopchenko
O V
OV
Gaspar'yan
A V
AV
Gershtein
E S
ES
Krasil'nikov
M A
MA
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology
D000970:Antineoplastic Agents; D013629:Tamoxifen; D004958:Estradiol