Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regular RIN1 gene is a molecule located on chromosome 1lq13.2, and contains a coding region of 2352 bp with a 3' domain that binds to H-Ras protein, suggesting that it is an important molecule in the intracellular signaling pathway. In this study, we confirmed the existence of a novel form of the RIN1 gene with a different splicing pattern, successfully cloned it, and examined its expression in gastric and colon cancer cell lines. A 612-bp band (the RIN1 variant mRNA) was identified in the RT-PCR product from the colon cancer cell line Colo320D. (A 2352-bp band representing the regular RIN1 gene in HT29 cell line.) The 612-bp band was sequenced and compared with that of the regular RIN1 gene. As a result, the 612-bp product was found to contain a tyrosine phosphorylation site on the 5' side and Ras and 14-3-3 binding domains on the 3' side, indicating that it is a product with a different splicing pattern. The expression of the RIN1 variant mRNA was observed in two of six gastric cancer cell lines and four of five colon cancer cell lines. We identified a novel RIN1 gene with a splicing pattern different from that of the regular RIN1 gene. Comparison of both genes revealed that the novel RIN1 products had a structure conserving the Ras and 14-3-3 binding domains, but lacking two tyrosine phosphorylation sites. Novel RIN1 variant protein was expressed primarily in the cytoplasm and no expression in the cell membrane, and RIN1 variant protein was bound to 14-3-3 protein. In addition, the novel RIN1 mRNA was found to be expressed in gastric and colon cancer cell lines, suggesting that it is an important gene for the function of cancer cells.
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PMID:Cloning of a novel splicing variant of RIN1 and its expression in gastric and colon cancer. 1980 90

The RIN1 protein has SH2, three domains, and H-Ras binding domains; thus, it is presumed to be an important molecule in an intracellular signaling pathway. We examined the effect of the introduction of a membrane protein-encoding, mutated (S351A)RIN1 gene into a colon cancer. In the LoVo colon cancer cell line, endogenous RIN1 protein was strongly expressed in the cytoplasmic fraction, and the RIN1 protein in the cytoplasmic fraction was strongly bound to the 14-3-3 protein. In the mutated (S351A)RIN1-transfected LoVo cells, the mutated (S351A)RIN1 protein was identified in the cell membrane, and was bound to HRas protein. Also, in vitro the proliferative capacity of the mutated (S351A)RIN1-transfected LoVo cells was significantly inhibited, compared with that of their empty vector-transfected counterparts. In the mutated (S351A)RIN1-transfected LoVo cells, the phosphorylation of ERK1/2 proteins downstream of the H-Ras molecule was inhibited, compared with the counterparts. This study is the first to show that the localization of RIN1 protein plays an important role in the carcinogenesis in colon cancer cells LoVo (i.e., signal transduction in the Ras-ERK pathway).
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PMID:RIN1-Ras-ERK pathway plays an important role in carcinogenesis in colon cancer cell line LoVo. 2281 85