Insulin‐like growth factor binding protein‐related protein 1 (IGFBP‐rP1) has potential tumour‐suppressive activity in human lung cancer

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Abstract
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 © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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