title: Reg protein is overexpressed in gastric cancer cells, where it activates a signal transduction pathway that converges on ERK1/2 to stimulate growth.
abstract: Reg is a growth factor with mitogenic effects on pancreatic beta cells and gastric stem cells. To date, there has been no information available on Reg-mediated intracellular signal transduction pathways. The role of Reg in the gastric carcinogenesis is also unknown. In the current study, the Reg signaling pathway in gastric cancer cell was examined. Reg treatment of MKN45 gastric cancer cells resulted in tyrosyl-phoshorylation of several cellular proteins and subsequent activation of classical MAPK, ERK1/2. Reg also stimulated thymidine incorporation in MKN45 and AGS gastric cancer cells in a dose-dependent manner. Finally, Reg was shown to be highly expressed in a large number of gastric cancers in vivo. Taken together, these data suggest that gastric cancer cells have gained the ability to overexpress Reg protein, which confer upon themselves added proliferative capacities, resulting in a considerable growth advantage.
authors.affiliation: Second Department of Internal Medicine, Shimane Medical University, Izumo 693-8501, Japan. y-kado@momo.so-net.ne.jp
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Youichi
authors.initials: Y
authors.lastname: Miyaoka
authors.forename: Mohammed Azharul Karim
authors.initials: MA
authors.lastname: Rumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kazumori
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Adachi
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002455:Cell Division; D017931:DNA Primers; D006133:Growth Substances / Q000378:metabolism* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D017931:DNA Primers; D006133:Growth Substances; D014443:Tyrosine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases