Reg protein is overexpressed in gastric cancer cells, where it activates a signal transduction pathway that converges on ERK1/2 to stimulate growth.
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.
Kadowaki
Yasunori
Y
Second Department of Internal Medicine, Shimane Medical University, Izumo 693-8501, Japan. y-kado@momo.so-net.ne.jp
Ishihara
Shunji
S
Miyaoka
Youichi
Y
Rumi
Mohammed Azharul Karim
MA
Sato
Hiroshi
H
Kazumori
Hideaki
H
Adachi
Kyoichi
K
Takasawa
Shin
S
Okamoto
Hiroshi
H
Chiba
Tsutomu
T
Kinoshita
Yoshikazu
Y
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
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