[Hypomethylation of 5'CpG island of insulin-like growth factor binding protein-related protein 1 is associated with its overexpression in colorectal cancer].
OBJECTIVE
To 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.


METHODS
Semi-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.


RESULTS
At 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.


CONCLUSIONS
IGFBP-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.
Lin
Jie
J
Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310058, China. lmd@zju.edu.cn
Zhu
Yi-Min
YM
Shao
Li-Na
LN
Huang
Qiong
Q
Lai
Mao-de
MD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000639:trends; D014158:Transcription, Genetic
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; C102529:insulin-like growth factor binding protein-related protein 1; D000077209:Decitabine; D001374:Azacitidine