Enhanced RASGEF1A expression is involved in the growth and migration of intrahepatic cholangiocarcinoma.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Ura
Katsuaki
K
Laboratory of Molecular Medicine and Promotion of Genome-Based Medicine Project, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Obama
Kazutaka
K
Satoh
Seiji
S
Sakai
Yoshiharu
Y
Nakamura
Yusuke
Y
Furukawa
Yoichi
Y
D000818:Animals; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000166:cytology / Q000378:metabolism; D019556:COS Cells; D002465:Cell Movement; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism* / Q000502:physiology*
D009363:Neoplasm Proteins; C516782:RASGEF1A protein, human; D020663:ras Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate; D015689:Oncogene Protein p21(ras)