guanosine-diphosphate and Bile-Duct-Neoplasms

To identify novel molecular targets for the treatment of intrahepatic cholangiocarcinoma (ICC), the second most common type of primary hepatobiliary cancer, we earlier analyzed genome-wide expression profiles of genes in 25 ICCs. Among the genes whose expression levels were commonly elevated in the tumors, we identified a novel gene termed RASGEF1A that encodes a putative Ras guanine nucleotide exchange factor domain-containing protein.. We showed in this article that RASGEF1A protein has a guanine nucleotide exchange activity to K-RAS, H-RAS, and N-RAS proteins in vitro. Consistently, exogenous RASGEF1A expression increased the activity of Ras. In addition, suppression of RASGEF1A by small interfering RNA retarded the growth of cholangiocarcinoma cells. Interestingly, COS7 cells expressing exogenous RASGEF1A showed enhanced cellular motility in Transwell and wound-healing assays.. These data suggest that elevated expression of RASGEF1A may play an essential role for proliferation and progression of ICC. Our data indicate that RASGEF1A may be a promising therapeutic target for the majority of ICCs.

Topics: Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cell Movement; Cell Proliferation; Chlorocebus aethiops; Cholangiocarcinoma; COS Cells; Gene Expression Regulation, Neoplastic; Guanosine Diphosphate; Humans; Mice; Neoplasm Proteins; NIH 3T3 Cells; Oncogene Protein p21(ras); ras Guanine Nucleotide Exchange Factors