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学科主题: 临床医学
题名:
Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas
作者: 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
发表日期: 2004-10-04
DOI: 10.1038/sj.bjc.6602127
卷: 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:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60008
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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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:
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.
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