Gastrin suppresses the interdependent expression of p16 and anion exchanger 1 favoring growth inhibition of gastric cancer cells.
Our previous studies demonstrated that expression and interaction of p16 with anion exchanger 1 (AE1) in gastric cancer cells is correlated with progression and shorter survival of the cancer. In this article, the effects of gastrin on p16 and AE1 and its implication in prevention and treatment of gastric cancer were studied by molecular biology techniques, animal experiment and clinical analysis. The results showed that expression of p16 in human gastric body carcinoma was downregulated along with the progression of the cancer, suggesting the reverse correlations between gastrin and p16 in vivo. Further experiments indicated that gastrin suppressed the expression of p16 via the p16 promoter and thereafter resulted in the degradation of AE1 in gastric cancer cells. Silencing of AE1 or p16 significantly inhibited the proliferation of the cancer cells. Using a xenograft tumor model in nude mice, we showed that experimental systemic hypergastrinemia induced by the administration of omeprazole led to decreased expression of AE1 and p16 as well as to a marked growth inhibition of SGC7901 tumors. It is concluded that a moderate plasma gastrin level is beneficial to the growth inhibition of gastric cancer by suppressing the expression of AE1 and p16. This finding may have an important implication for the prevention and treatment of cancers arise in the gastric antrum.
Tian
Hua
H
Department of Pathology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Zhang
Ning
N
Suo
Wen-Hao
WH
Wang
Ting
T
Song
Ling-Jun
LJ
Wu
Jun
J
Liu
Qiang
Q
Shen
Wei-Wei
WW
Fu
Guo-Hui
GH
D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D015536:Down-Regulation; D005755:Gastrins / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001457:Anion Exchange Protein 1, Erythrocyte; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D005755:Gastrins; D009363:Neoplasm Proteins