Hypomethylation of 5'CpG island of insulin-like growth factor binding protein-related protein 1 is associated with its overexpression in colorectal cancer.
- Author:
Jie LIN
1
;
Yi-Min ZHU
;
Li-Na SHAO
;
Qiong HUANG
;
Mao-de LAI
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Aged, 80 and over; Azacitidine; analogs & derivatives; pharmacology; Cell Line, Tumor; Colorectal Neoplasms; genetics; CpG Islands; physiology; DNA Methylation; Female; Gene Expression Regulation, Neoplastic; Humans; Insulin-Like Growth Factor Binding Proteins; genetics; Male; Middle Aged; RNA, Messenger; metabolism; Reverse Transcriptase Polymerase Chain Reaction; trends; Transcription, Genetic
- From: Chinese Journal of Pathology 2008;37(8):512-516
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the methylation status of 5'CpG island of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) in colorectal cancer and its relationship with gene expression and clinicopathologic parameters.
METHODSSemi-quantitative reverse transcription-PCR (RT-PCR) was used to detect the expression of IGFBP-rP1 in 46 cases of colorectal cancer and their matched normal mucosa. Methylation-specific PCR (MSP) was applied to evaluate the methylation status of 5'CpG island of IGFBP-rP1. Colon cancer cell lines LoVo and SW620 were treated with demethylation agent 5-aza-2'-deoxycytidine (5-aza-dC), followed by RT-PCR and MSP detection.
RESULTSAt the mRNA level, the expression of IGFBP-rP1 was higher in colorectal cancer tissue than that in the matched normal mucosa (P < 0.05). IGFBP-rP1 was methylated in 28/46 (60.9%) cases of colorectal cancer and 37/46 (80.4%) matched normal mucosa samples (P < 0.05). A negative correlation was found between IGFBP-rP1 expression and its methylation status. The expression of IGFBP-rP1 was restored in LoVo and SW620 after treatment with 5-aza-dC and MSP confirmation of its demethylation status. No relationships was found between the methylation status and clinicopathologic parameters.
CONCLUSIONSIGFBP-rP1 expression is negatively correlated with its methylation status in colorectal cancer. DNA methylation is one of the mechanisms regulating the expression of IGFBP-rP1. Hypomethylation of IGFBP-rP1 gene with its overexpression plays an important role in the initiation and development of colorectal cancer.