Expression and functional role of inhibitor-of-apoptosis protein livin (BIRC7) in neuroblastoma

被引：42

作者：

Dasgupta, Anindya ^{[1
]}

Alvarado, Carlos S. ^{[1
]}

Xu, Zhiheng ^{[2
]}

Findley, Harry W. ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA

[2] Emory Univ, Rollins Sch Publ Hlth, Winship Canc Inst, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 400卷 / 01期

关键词：

Neuroblastoma; Livin; MYCN; Drug resistance; Gene silencing; Apoptosis; MELANOMA INHIBITOR; ML-IAP; CELLS; GENE; SURVIVIN; TARGET; MYCN; RNA;

D O I：

10.1016/j.bbrc.2010.08.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We evaluated the expression of the inhibitor-of-apoptosis protein (IAP) livin (BIRC7) in 59 cases of neuroblastoma (NBL) by quantitative RT-PCR. We also examined the role of livin in protecting tumor cells from chemotherapy drugs. Livin expression varied significantly among tumors. High levels of expression were observed in 17 of 39 patients with advanced stages (stages 3 and 4) and 6 of 20 patients with localized stages (stages 1 and 2). Livin-transfected, MYCN-amplified NBL cells showed increased resistance to doxorubicin and etoposide. Conversely, livin knockdown with siRNA enhanced spontaneous and drug-induced apoptosis in NBL cells. Multivariate analysis of prognostic factors showed that high livin expression worsened prognosis for patients with MYCN-amplified tumors. Our data suggest that (i) livin is frequently expressed in NBL and protects tumor cells with amplified MYCN oncogene from genotoxic agents; (ii) the antiapoptotic effect of livin in NBL is blocked by siRNA; (iii) in the sample studied, high livin expression enhanced the adverse prognostic impact of MYCN amplification. These findings suggest that livin may contribute to drug resistance in NBL. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：53 / 59

页数：7

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