Hypomethylation of 5'CpG island of insulin-like growth factor binding protein-related protein 1 is associated with its overexpression in colorectal cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Study of B2 gene structure and its expression in colorectal cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To get a complete cDNA sequence of B2 and evaluate the correlation on structure and expression between B2 and insulin like growth factor binding protein related protein 1 (IGFBP-rP1) in colorectal carcinomas, paired normal tissues, adenomas, tissues adjacent to the tumor, and colorectal carcinoma cell lines.</p><p><b>METHODS</b>5'RACE (rapid amplification of cDNA end) was applied to get the sequence of the 5' end of B2. Semi-quantitative RT-PCR and immunohistochemistry were used to detect the expression of B2 in colorectal cancer tissues and cell lines (SW480, SW1116, SW620, HCT8, CoLo205 and LoVo).</p><p><b>RESULTS</b>A sequence of 1,125 bp was obtained by combining the sequence from 5'RACE product and the known sequence of B2. It shared 1,122/1,125 identities with IGFBP-rP1. At the level of mRNA, the expression of B2/IGFBP-rP1 was high in colorectal carcinomas, moderate in adenomas and tissues adjacent to tumor, low in normal tissues (P < 0.05). Five cell lines except SW480 showed no expression of B2/IGFBP-rP1. A significant difference was obtained in the immunoreactivity of B2/IGFBP-rP1 between normal tissue and cancer (P < 0.05). In 28.9% (22/76) samples, cancer cells locating at the invasive front of cancer nest had a stronger staining of B2/IGFBP-rP1 than those surrounding the lumen. These samples had also an increased frequency of lymph node metastases, increased depth of invasion and a stronger staining of B2/IGFBP-rP1 than in other samples (P < 0.05).</p><p><b>CONCLUSIONS</b>B2 is the same gene as IGFBP-rP1. Overexpression of B2/IGFBP-rP1 may play an important role in the initiation and promotion of colorectal cancer. Its overexpression in invading tumor cells may be linking with an increased potential of invasion.</p>