Expression and functional role of inhibitor-of-apoptosis protein livin (BIRC7) in neuroblastoma.
We evaluated the expression of the inhibitor-of-apoptosis protein (IAP)livin (BIRC7)in 59 cases ofneuroblastoma (NBL) by quantitative RT-PCR. We also examined the role of livin in protecting tumor cells from chemotherapy drugs. Livin expression varied significantly amongtumors. 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.
Dasgupta
Anindya
A
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Alvarado
Carlos S
CS
Xu
Zhiheng
Z
Findley
Harry W
HW
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002648:Child; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering