Insulin-like growth factor binding protein-related protein I (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer
Insulin-like growth factor binding protein-related protein I (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer
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DOI：
10.1002/path.2132
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发表时间：
2007-03-01
影响因子：
7.3
通讯作者：
Petersen, I.
中科院分区：
文献类型：
--
作者：
Chen, Y.;Pacyna-Gengelbach, M.;Petersen, I.
胰岛素样生长因子结合蛋白相关蛋白1 （IGFBP-rP1）在多种肿瘤中表达降低，但IGFBP-rP1在肺癌中的作用尚不清楚。本研究检测了IGFBP-rP1在肺癌细胞系中的表达，发现IGFBP-rP1表达降低。通过免疫组化分析，在包含138个原发肿瘤和20个正常肺组织的组织微阵列中，58个肿瘤（42%）未表达IGFBP-rP1，而20个正常肺组织均高表达。在鳞状细胞肺癌中，IGFBP-rP1的低表达与高级别肿瘤显著相关。用5-aza-2'-脱氧胞苷治疗后，四种肺癌细胞系中的三种恢复了IGFBP-rP1的表达。亚硫酸钠处理的三种肺癌细胞系基因组DNA的PCR产物测序显示，外显子1和内含子1区域存在异质甲基化模式。将IGFBP-rP1全长cDNA稳定转染到H2170肺癌细胞系中，IGFBP-rP1蛋白的表达增加。igfbp - rp1阳性转染物在软琼脂中的集落形成能力显著降低，在裸鼠体内的肿瘤生长速率受到抑制，凋亡细胞数量增加，激活caspase-3表达水平。这些数据表明IGFBP-rP1在人肺癌中是一种被DNA甲基化失活的肿瘤抑制因子。版权所有(c) 2007大不列颠和爱尔兰病理学会。
The expression of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is decreased in various tumours, but the role of IGFBP-rP1 in lung cancer is not yet clear. In this study, IGFBP-rP1 expression in lung cancer cell lines was evaluated and reduced expression of IGFBP-rP1 was found. In tissue microarrays containing 138 primary tumours and 20 normal lung tissues analysed by immunohistochemistry, 58 tumours (42%) exhibited no expression of IGFBP-rP1, while all 20 normal lung tissues showed high expression. In squamous cell lung cancer, low expression of IGFBP-rP1 was significantly linked to high-grade tumours. Treatment with 5-aza-2'-deoxycytidine restored the expression of IGFBP-rP1 in three of four lung cancer cell lines. Sequencing of PCR products of sodium bisulphite-treated genomic DNA from the three lung cancer cell lines revealed a heterogeneous methylation pattern in the region of exon 1 and intron 1. Stable transfection of IGFBP-rP1 full-length cDNA into the H2170 lung cancer cell line led to increased expression of IGFBP-rP1 protein. IGFBP-rP1-positive transfectants exhibited remarkably reduced colony-forming ability in soft agar, suppression of tumour growth rate in nude mice, and increased apoptotic cell number as well as activated caspase-3 expression level. The data suggest that IGFBP-rP1 is a tumour suppressor inactivated by DNA methylation in human lung cancer. Copyright (c) 2007 Pathological Society of Great Britain and Ireland.