Downregulation of Smac/DIABLO expression in renal cell carcinoma and its prognostic significance.

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摘要：

PURPOSE: /direct inhibitor of apoptosis-with low pI (/) was recently identified as a that is released from in response to apoptotic stimuli and promotes apoptosis by antagonizing . Furthermore, /plays an important regulatory role in the of to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of /in various , including renal (RCC). This study examined /expression in 78 healthy kidneys and 78 RCCs.: The level of /expression was quantified by Western blot analysis using nonfixed fresh frozen tissues.: The expression of /was lower in RCC compared with the autologous normal kidney. Sixty-four (82%) of 78 of RCC expressed /, and 18% were negative, whereas 100% of normal kidney tissues were positive. In stage I/II RCC, 96% expressed /, whereas only 50% expressed /in stage III/IV. /expression inversely correlated with the grade of RCC. Patients with RCC expressing /had a longer postoperative disease-specific survival than those without /expression in the 5-year follow-up. Transfection with /cDNA enhanced -related apoptosis-inducing ligand (TRAIL) -mediated and -mediated cytotoxicity in RCC.: The present study demonstrates for the first time that /expression was downregulated in RCC and that no /expression in RCC predicted a worse prognosis. In addition, transfection with /sensitized RCC to TRAIL/-induced apoptosis. These results suggest that /expression in RCC may be used as a prognostic parameter, and that enhancement of /expression in RCC may potentiate immunotherapy and chemotherapy.

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关键词：

Cell

DOI：

10.1200/JCO.2005.02.191

被引量：

290

年份：

2005