The anti-apoptotic livin gene is an important determinant for the apoptotic resistance of non-small cell lung cancer cells.
Cancer cells are typically characterized by increased resistance towards apoptosis. Livin (alternatively called ML-IAP or KIAP) is an anti-apoptotic protein which is expressed in several cancer forms. Using real-time reverse transcription-polymerase chain reaction (RT-PCR), we confirmed livin expression in a significant portion of non-small cell lung cancer (NSCLC) tissue samples and, in addition, detected livin expression in a number of NSCLC cell lines. In order to elucidate whether livin contributes to the apoptotic resistance of lung cancer cells, we silenced endogenous livin expression in a panel of cancer-derived NSCLC cell lines by RNA interference (RNAi). We observed that the targeted inhibition of livin strongly sensitized NSCLC cells to different pro-apoptotic stimuli, such as UV-irradiation or the chemotherapeutic drug etoposide. In addition, long-term silencing of livin blocked the outgrowth of NSCLC cells in colony formation assays. These effects of small interfering (si)RNA were specific for livin-expressing tumor cells. Our results indicate that Livin is an important contributor to the apoptosis resistance of NSCLC cells and may serve as a novel molecular target for therapeutic inhibition in NSCLC.
Crnković-Mertens
Irena
I
Deutsches Krebsforschungszentrum, Molekulare Therapie Virus-assoziierter Tumore (F065), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany.
Muley
Thomas
T
Meister
Michael
M
Hartenstein
Bettina
B
Semzow
Julia
J
Butz
Karin
K
Hoppe-Seyler
Felix
F
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000503:physiopathology*; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000502:physiology*; D008175:Lung Neoplasms / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D014162:Transfection; D014410:Tumor Stem Cell Assay; D014466:Ultraviolet Rays
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D005047:Etoposide