TI - Gastrin-mediated activation of cyclin D1 transcription involves beta-catenin and CREB pathways in gastric cancer cells . AB - Gastrin and its precursors promote proliferation in different gastrointestinal cells . Since mature , amidated gastrin ( G-17 ) can induce cyclin D1 , we determined whether G-17 -mediated induction of cyclin D1 transcription involved Wnt signaling and CRE-binding protein ( CREB ) pathways . Our studies indicate that G-17 induces protein , mRNA expression and transcription of the G(1) -specific marker cyclin D1 , in the gastric adenocarcinoma cell line AGSE ( expressing the gastrin/cholecystokinin B receptor ) . This was associated with an increase in steady-state levels of total and nonphospho beta-catenin and its nuclear translocation , indicating the activation of the Wnt -signaling pathway . In addition , G-17 -mediated increase in cyclin D1 transcription was significantly attenuated by axin or dominant-negative ( dn ) T-cell factor 4 ( TCF4 ) , suggesting crosstalk of G-17 with the Wnt -signaling pathway . Mutational analysis indicated that this effect was mediated through the cyclic AMP response element ( CRE ) ( predominantly ) and the TCF sites in the cyclin D1 promoter , which was also inhibited by dnCREB . Furthermore , G-17 stimulation resulted in increased CRE-responsive reporter activity and CREB phosphorylation , indicating an activation of CREB . Chromatin immunoprecipitation studies revealed a G-17 -mediated increase in the interaction of beta-catenin with cyclin D1 CRE , which was attenuated by dnTCF4 and dnCREB . These results indicate that G-17 induces cyclin D1 transcription , via the activation of beta-catenin and CREB pathways .