Downregulation of Smac/DIABLO expression in renal cell carcinoma and its prognostic significance.
J Clin Oncol
; 23(3): 448-54, 2005 Jan 20.
Article
em En
| MEDLINE
| ID: mdl-15572731
ABSTRACT
PURPOSE:
Second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of Smac/DIABLO in various cancers, including renal cell carcinoma (RCC). This study examined Smac/DIABLO expression in 78 healthy kidneys and 78 RCCs. MATERIALS ANDMETHODS:
The level of Smac/DIABLO expression was quantified by Western blot analysis using nonfixed fresh frozen tissues.RESULTS:
The expression of Smac/DIABLO was lower in RCC compared with the autologous normal kidney. Sixty-four (82%) of 78 of RCC expressed Smac/DIABLO, and 18% were negative, whereas 100% of normal kidney tissues were positive. In stage I/II RCC, 96% expressed Smac/DIABLO, whereas only 50% expressed Smac/DIABLO in stage III/IV. Smac/DIABLO expression inversely correlated with the grade of RCC. Patients with RCC expressing Smac/DIABLO had a longer postoperative disease-specific survival than those without Smac/DIABLO expression in the 5-year follow-up. Transfection with Smac/DIABLO cDNA enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) -mediated and cisplatin-mediated cytotoxicity in RCC.CONCLUSION:
The present study demonstrates for the first time that Smac/DIABLO expression was downregulated in RCC and that no Smac/DIABLO expression in RCC predicted a worse prognosis. In addition, transfection with Smac/DIABLO sensitized RCC to TRAIL/cisplatin-induced apoptosis. These results suggest that Smac/DIABLO expression in RCC may be used as a prognostic parameter, and that enhancement of Smac/DIABLO expression in RCC may potentiate immunotherapy and chemotherapy.
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
/
Proteínas de Transporte
/
Biomarcadores Tumorais
/
Regulação Neoplásica da Expressão Gênica
/
Proteínas Mitocondriais
/
Neoplasias Renais
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article