title: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has potential tumour-suppressive activity in human lung cancer.
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.
authors.affiliation: Institute of Pathology, University Hospital Charité, Schumannstr 20-21, D-10098 Berlin, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Pacyna-Gengelbach
authors.forename: F
authors.initials: F
authors.lastname: Ye
authors.forename: T
authors.initials: T
authors.lastname: Knösel
authors.forename: P
authors.initials: P
authors.lastname: Lund
authors.forename: N
authors.initials: N
authors.lastname: Deutschmann
authors.forename: K
authors.initials: K
authors.lastname: Schlüns
authors.forename: W F M A
authors.initials: WF
authors.lastname: Kotb
authors.forename: C
authors.initials: C
authors.lastname: Sers
authors.forename: H
authors.initials: H
authors.lastname: Yasumoto
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: I
authors.initials: I
authors.lastname: Petersen
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics; D017209:Apoptosis / Q000502:physiology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004273:DNA, Neoplasm / Q000235:genetics; D000077209:Decitabine; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis*; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods; D009367:Neoplasm Staging; D014162:Transfection / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000032:analysis*
chemical_list: D004273:DNA, Neoplasm; D018969:Insulin-Like Growth Factor Binding Proteins; D025521:Tumor Suppressor Proteins; C102529:insulin-like growth factor binding protein-related protein 1; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine