Overcoming resistance to trail-induced apoptosis in prostate cancer by regulation of c-FLIP.
Using Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL) for cancer therapy is attractive, because TRAIL is effective against cancer cells without inducing significant cytotoxicity, making it an ideal cancer drug. However, some cancer cells evade TRAIL-induced apoptosis and become resistant. We have been investigating the molecular mechanisms that differentiate between TRAIL-resistant and TRAIL-sensitive prostate cancer cells. We have found that transcriptional regulation of the anti-apoptotic molecule, c-FLIP(L), can regulate sensitivity of cancer cells to TRAIL. We have found that c-Fos, represses expression of c-FLIP(L), and promotes TRAIL-induced apoptosis. Identifying molecular mechanisms that differentiate between sensitive and resistant cancer cells will help improve pro-apoptotic cancer therapies.
Zhang
Xiaoping
X
Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Li
Wenhua
W
Olumi
Aria F
AF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse