Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis |
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Authors: | I Crnković-Mertens N Wagener J Semzow E F Gröne A Haferkamp M Hohenfellner K Butz F Hoppe-Seyler |
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Institution: | (1) German Cancer Research Center, Molecular Therapy of Virus-Associated Cancers (F065), Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany;(2) Department of Urology, University of Heidelberg, 69120 Heidelberg, Germany;(3) Cellular and Molecular Pathology (E090), German Cancer Research Center, 69120 Heidelberg, Germany |
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Abstract: | 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.
Received 30 November 2006; received after revision 22 February 2007; accepted 20 March 2007 |
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Keywords: | Apoptosis regulation Livin/ML-IAP inhibitor of apoptosis proteins renal cell cancer RNA interference |
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