Peer-Reviewed Journal Details
Mandatory Fields
Curtin, JF,Cotter, TG;
2003
March
British Journal of Cancer
Defects in death-inducing signalling complex formation prevent JNK activation and Fas-mediated apoptosis in DU 145 prostate carcinoma cells
Validated
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Optional Fields
CD95 apoptosis FADD DAXX HSP27 JNK SHOCK-PROTEIN 27 CANCER CELLS KINASE DAXX HSP27 EXPRESSION FAS/APO-1 PATHWAY ASK1 DISC
89
1950
1957
Androgen-independent prostate carcinomas are resistant to chemotherapy and cell lines derived from androgen-independent prostate carcinomas such as DU 145 cells are highly resistant to Fas-mediated apoptosis. The incubation of DU 145 cells with anti-Fas IgM agonistic antibody of Fas receptor fails to activate JNK, a stress kinase involved in regulating apoptosis. We have previously shown that JNK activation is sufficient and necessary to promote Fas-mediated apoptosis in DU 145 cells. We investigate the mechanisms by which JNK activation and apoptosis are abrogated. HSP27 is overexpressed in DU 145 cells and has previously been reported to sequester DAXX and prevent JNK activation in cells treated with anti-Fas IgM. However, we find no evidence that HSP27 interacts with DAXX in DU 145 cells. Instead, we find that FADD does not interact with caspase-8 and this results in defective death-inducing signalling complex formation following Fas receptor activation.
DOI 10.1038/sj.bjc.6601393
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