Oestrogen-mediated suppression of tumour necrosis factor alpha-induced apoptosis in MCF-7 cells: subversion of Bcl-2 by anti-oestrogens.
In oestrogen receptor (ER)-positive breast carcinoma cells, 17beta-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.
Burow
M E
ME
Center for Bioenvironmental Research, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Weldon
C B
CB
Tang
Y
Y
McLachlan
J A
JA
Beckman
B S
BS
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D019254:Genes, bcl-2; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D020847:Estrogen Receptor Modulators; D014409:Tumor Necrosis Factor-alpha; D000077267:Fulvestrant; D004958:Estradiol; D004317:Doxorubicin; D020928:Mitogen-Activated Protein Kinases; D017239:Paclitaxel