Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis

被引：82

作者：

Crnkovic-Mertens, I.

Wagener, N.

Semzow, J.

Groene, E. F.

Haferkamp, A.

Hohenfellner, M.

Butz, K.

Hoppe-Seyler, F.

机构：

[1] German Canc Res Ctr, D-69120 Heidelberg, Germany

[2] Heidelberg Univ, Dept Urol, D-69120 Heidelberg, Germany

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2007年 / 64卷 / 09期

关键词：

apoptosis regulation; livin/ML-IAP; inhibitor of apoptosis proteins; renal cell cancer; RNA interference;

D O I：

10.1007/s00018-007-6510-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

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收藏

页码：1137 / 1144

页数：8

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