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学科主题临床医学
Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas
Yan, Y; Mahotka, C; Heikaus, S; Shibata, T; Wethkamp, N; Liebmann, J; Suschek, CV; Guo, Y; Gabbert, HE; Gerharz, CD; Ramp, U
关键词X-linked Inhibitor Of Apoptosis Second Mitochondria-derived Activator Of Caspases Direct Iap-binding Protein With Low Pi Renal Cell Carcinoma Tumour Progression
刊名BRITISH JOURNAL OF CANCER
2004-10-04
DOI10.1038/sj.bjc.6602127
91期:7页:1349-1357
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]X-LINKED INHIBITOR ; CD95 (APO-1/FAS)-MEDIATED APOPTOSIS ; SURVIVIN SPLICE VARIANTS ; LIGAND-INDUCED APOPTOSIS ; LUNG-CANCER PATIENTS ; HUMAN OVARIAN-CANCER ; SERINE-PROTEASE ; IAP PROTEINS ; PROGNOSTIC-SIGNIFICANCE ; CASPASE ACTIVITY
英文摘要

Dysregulation of apoptosis plays an important role in tumour progression and resistance to chemotherapy. The X-linked inhibitor of apoptosis ( XIAP) is considered to be the most potent caspase inhibitor of all known inhibitor of apoptosis-family members. Only recently, an antagonist of XIAP has been identified, termed Smac/DIABLO. To explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs), we analysed XIAP and Smac/DIABLO mRNA and protein expression in the primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA. X-linked inhibitor of apoptosis and Smac/DIABLO mRNA expression was found in all RCCs. Importantly, the relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages ( P = 0.0002) and also with tumour dedifferentiation ( P = 0.04). Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. Consequently, the mRNA expression ratio between antiapoptotic XIAP and proapoptotic Smac/DIABLO markedly increased during progression from early ( pT1) to advanced ( pT3) tumour stages. Moreover, RCCs confined within the organ capsule ( pT1 and pT2) exhibited a significantly lower XIAP to Smac/DIABLO expression ratio when compared with RCCs infiltrating beyond the kidney ( pT3; P = 0.01). Thus, our investigation demonstrates that the delicate balance between XIAP and Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of antiapoptotic XIAP over proapoptotic Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.

语种英语
WOS记录号WOS:000224250400019
Citation statistics
Cited Times:57[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60008
Collection北京大学第一临床医学院_泌尿外科
作者单位1.Univ Hosp, Inst Mol Med, Dusseldorf, Germany
2.Peking Univ, Hosp 1, Inst Urol, Beijing, Peoples R China
3.Univ Hosp, Inst Pathol, Dusseldorf, Germany
Recommended Citation
GB/T 7714
Yan, Y,Mahotka, C,Heikaus, S,et al. Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas[J]. BRITISH JOURNAL OF CANCER,2004,91(7):1349-1357.
APA Yan, Y.,Mahotka, C.,Heikaus, S.,Shibata, T.,Wethkamp, N.,...&Ramp, U.(2004).Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas.BRITISH JOURNAL OF CANCER,91(7),1349-1357.
MLA Yan, Y,et al."Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas".BRITISH JOURNAL OF CANCER 91.7(2004):1349-1357.
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