Affiliation: | a Center for Bioenvironmental Research, Tulane University Health Sciences Center, New Orleans, LA 70112, USA b Molecular and Cellular Biology Program, Tulane University Health Sciences Center, New Orleans, LA 70112, USA c Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA d Tulane Cancer Center, Tulane University Health Sciences Center, New Orleans, LA 70112, USA e Department of Surgery, Tulane University Medical Center, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL-83, New Orleans, LA 70112, USA f Department of Environmental Health Sciences, Tulane University Health Sciences Center, New Orleans, LA 70112, USA |
Abstract: | In oestrogen receptor (ER)-positive breast carcinoma cells, 17β-oestradiol suppresses a dose-dependent induction of cell death by tumour necrosis factor alpha (TNF). The ability of oestrogens to promote cell survival in ER-positive breast carcinoma cells is linked to a coordinate increase in Bcl-2 expression, an effect that is blocked with the pure anti-oestrogen ICI 182,780. The role of Bcl-2 in MCF-7 cell survival was confirmed by stable overexpression of Bcl-2 which resulted in suppression of apoptosis induced by doxorubicin (DOX), paclitaxel (TAX) and TNF as compared to vector-control cells. The pure anti-oestrogen ICI 182,780 in combination with TNF, DOX or TAX potentiated apoptosis in vector-transfected cells. Interestingly, pre-treatment with ICI 182,780 markedly enhanced chemotherapeutic drug- or TNF-induced apoptosis in Bcl-2 expressing cells, an effect that was correlated with ICI 182,780 induced activation of c-Jun N-terminal kinase. Our results suggest that the effects of oestrogens/anti-oestrogens on the regulation of apoptosis may involve coordinate activation of signalling events and Bcl-2 expression. |