NF-kappaB suppression provokes the sensitization of hormone-resistant breast cancer cells to estrogen apoptosis.
The progression of breast cancer cells to estrogen-independent growth may be accompanied with the paradoxical cell sensitization to estrogen apoptotic action; however, the mechanism of this phenomenon is still unclear. In the present study, we have shown that the sensitization of hormone-resistant breast cancer cells to estrogen apoptotic action is accompanied with the gradual NF-kappaB suppression. Using the chemical inhibitors of NF-kappaB as well as the dominant-negative NF-kappaB constructs, we have proved the sufficiency of NF-kappaB inhibition for the sensitization of the resistant cells to estrogen apoptosis. Estradiol treatment results in the additional suppression of NF-kappaB, demonstrating the possible NF-kappaB involvement in the regulation of cell response to estrogens. Totally, the results presented suggest that the constitutive NF-kappaB suppression in the estrogen-independent cells may be considered as one of the factors resulting in a imbalance between pro- and anti-apoptotic pathways and enhancement in estrogen apoptotic action in the cells.
Lobanova
Y S
YS
Laboratory of Molecular Endocrinology, Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Russian Academy of Medical Science, Kashirskoye shosse 24, Moscow, 115478, Russia.
Scherbakov
A M
AM
Shatskaya
V A
VA
Evteev
V A
VA
Krasil'nikov
M A
MA
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004351:Drug Resistance; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*
D004967:Estrogens; D006728:Hormones; D016328:NF-kappa B