Increased expression of insulin-like growth factor-II messenger RNA-binding protein 1 is associated with tumor progression in patients with lung cancer

被引:82
作者
Kato, Tatsuya
Hayama, Satoshi
Yamabuki, Takumi
Ishikawa, Nobuhisa
Miyamoto, Masaki
Ito, Tomoo
Tsuchiya, Eiju
Kondo, Satoshi
Nakamura, Yusuke
Daigo, Yataro
机构
[1] Univ Tokyo, Mol Med Lab, Ctr Human Genome, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan
[2] Hokkaido Univ, Grad Sch Med, Dept Surg Oncol, Sapporo, Hokkaido, Japan
[3] Hokkaido Univ, Grad Sch Med, Dept Surg Pathol, Sapporo, Hokkaido, Japan
[4] Kanagawa Canc Ctr, Res Inst, Kanagawa, Japan
关键词
D O I
10.1158/1078-0432.CCR-06-1297
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To identify novel biomarkers and therapeutic targets for lung cancers, we screened for genes that were highly transactivated in a large proportion of non-small cell lung cancers (NSCLC) using a cDNA microarray representing 27,648 genes. Experimental Design: A gene encoding insulin-like growth factor-II mRNA-binding protein 1 (IMP-1) was selected as a candidate (>= 3-folcl expression than in normal lung tissue in about 70% of NSCLCs). Tumor tissue microarray was applied to examine expression of IMP-1 protein in archival lung cancer samples from 267 patients and investigated its clinicopathologic significance. A role of IMP-1 in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of IMP-1 on mammalian cells was examined using Matrigel assays. mRNAs associated with IMP-1 in cancer cells were also isolated by RNA immunoprecipitation followed by cDNA microarray analysis. Results: Positive immunostaining of IMP-1 was correlated with male (P = 0.0001), tumor size (P = 0.0003), non-adenocarcinoma histology (P < 0.0001), smoking history (P = 0.0005), non - well-differentiated tumor grade (P = 0.0001), and poor prognosis (P = 0.0053). Suppression of IMP-1 expression with small interfering RNA effectively suppressed growth of NSCLC cells. In addition, we identified that exogenous expression of IMP-1 increased the migratory activity of mammalian cells. IMP-1 was able to bind to mRNAs encoding a variety of proteins involved in signal transduction, cell cycle progression, cell adhesion and cytoskeleton, and various types of enzymatic activities. Conclusions: These results suggest that IMP-1 expression is likely to play important roles in lung cancer development and progression, and that IMP-1 is a prognostic biomarker and a promising therapeutic target for lung cancer.
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页码:434 / 442
页数:9
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