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

RIN1基因位于染色体11q13.2上，是一个由2352 bp的编码区组成的分子，在3′侧有一个与H-Ras蛋白结合的结构域，被认为是细胞内信号通路的重要分子。由于属于H-Ras效应分子的RIN1分子迄今尚未在结直肠癌或其他消化道癌症中报道，因此我们研究了RIN1基因如何参与结直肠癌。101例结直肠癌标本中有52例（51.5%）与邻近正常结直肠组织相比强烈表达RIN1基因。RIN1基因表达阳性患者的5年生存率为55%，明显低于RIN1基因表达阴性患者的83%。此外，我们证实了RIN1蛋白主要定位于结直肠癌细胞系的细胞质中，并与14-3-3蛋白结合，而不与Ras蛋白结合。这些结果表明，RIN1基因是评价结直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.