Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis.
Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition, we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents.
Crnković-Mertens
I
I
German Cancer Research Center, Molecular Therapy of Virus-Associated Cancers (F065), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
Wagener
N
N
Semzow
J
J
Gröne
E F
EF
Haferkamp
A
A
Hohenfellner
M
M
Butz
K
K
Hoppe-Seyler
F
F
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000502:physiology*; D002292:Carcinoma, Renal Cell / Q000473:pathology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors*; D007680:Kidney Neoplasms / Q000473:pathology* / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000302:isolation & purification; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm