Regulation of RIG1 expression and its association with K-ras mutation in colorectal cancer cells

• Main Authors: Yao, Hsin-Tien, 姚欣田
• Other Authors: Jiang, Shun-Yuan
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/84868194965385254207

碩士 === 國防醫學院 === 微生物及免疫學研究所 === 92 === Colorectal cancer evolves through a multistep process in gene alterations. Mutated K-Ras was found in 45% of colorectal cancer in early development during adenomatous stage. Retinoid inducible gene 1 (RIG1) is a tumor suppressor gene isolated from retinoid-treated cells, which can negatively regulate downstream signal pathway of Ras and lead to growth suppression and apoptosis of several cancer cells. Here we analyzed the correlation between K-Ras mutation and RIG1 protein expression in paraffin-embedded colorectal cancer tissues, and investigated the regulation of RIG1 expression by the Ras signal pathways. Mutations at codon 12 and 13 of the K-Ras gene were found in 25 of 45 (55.5%) colorectal cancer tissues analyzed by DNA sequencing and muation-specific PCR. Twenty three out of the 25 (92%) tissues with K-Ras mutation were stained positive for RIG1 protein. Whereas, only 9 out of 20 (45%) tissues with wild type K-Ras expressed the RIG1 protein. RIG1 expression was positively correlated to tumor differentiation. Endogenous RIG1 expression was low in 8 colorectal cancer cell lines. Blockage of the ERK/ELK pathway by PD98059 (50μM) for 48 hours resulted in an enhanced RIG1 mRNA level in SW480 cells, and an increased RIG1 protein expression in SW480 and HT29 cells. Whereas, suppression of the PI3K/AKT pathway by LY294002 had no effect on RIG1 expression. High percentage of colorectal cancer tissues with K-Ras mutation were stained positive for RIG1 protein. However, results from in vitro data indicated down regulation of RIG1 expression through the ERK/ELK pathway in cells with K-Ras mutation. These observations suggest that RIG1 expressions were differently regulated between in vivo and in vitro by Ras signal pathways.