Analysis of H-Ras-RIN1 signaling cascade in colorectal cancer

RIN 1基因位于染色体11q13.2上，是由2352 bp的编码区组成的分子，在3 '侧具有与H-Ras蛋白结合的结构域，被推测是细胞内信号通路中的重要分子。由于属于H-Ras效应分子的RIN 1分子迄今尚未在结直肠癌或其他消化道癌中报道，我们研究了RIN 1基因如何参与结直肠癌。52例（51.5%）的101例结直肠癌标本强表达RIN 1基因相比，相邻的正常结直肠组织。RIN 1基因表达阳性患者的5年生存率为55%，明显低于RIN 1基因表达阴性患者的5年生存率（83%）。RIN 1蛋白主要定位于大肠癌细胞的胞浆中，与14-3-3蛋白结合，而与Ras蛋白不结合，提示RIN 1基因是评价大肠癌恶性程度的重要信号转导系统。

The RIN1 gene, located on chromosome 11q13.2, is a molecule consisting of a coding region of 2352 bp, has a domain on the 3'side that binds to H-Ras protein, and is presumed to be an important molecule in an intracellular signaling pathway. Since the RIN1 molecule belonging to the effector molecules of H-Ras has not been reported in colorectal or other digestive tract cancers to date, we investigated how the RIN1 gene was involved in colorectal cancer. Fifty-two (51.5%) of 101 colorectal cancer specimens strongly expressed the RIN1 gene compared to the adjacent normal colorectal tissue. The 5-year survival rate of patients positive for the expression of the RIN1 gene was significantly poorer at 55% than that (83%) of patients negative for the expression of the RIN1 gene. Also, We confirmed that RIN1 protein was localized chiefly in the cytoplasm of colorectal cancer cell line, and bound to 14-3-3 protein, but not to Ras protein.These results indicate that the RIN1 gene serves as an important signal transduction system for evaluating the malignancy of colorectal cancer.