title: Gastrin-induced gastric adenocarcinoma growth is mediated through cyclin D1.
abstract: Gastrin is a gastrointestinal (GI) peptide that possesses potent trophic effects on most of the normal and neoplastic mucosa of the GI tract. Despite abundant evidence for these properties, the mechanisms governing gastrin-induced proliferation are still largely unknown. To elucidate the mechanisms by which gastrin might influence mitogenesis in gastric adenocarcinoma, we analyzed its effects on the human cell line AGS-B. Amidated gastrin (G-17), one of the major circulating forms of gastrin, induced a concentration-dependent increase in [3H]thymidine incorporation of cells in culture, with the maximum effective concentration occurring with 20 nM G-17. This effect was significantly attenuated by the gastrin-specific receptor antagonist L-365260. In addition, we found that G-17 induced a significant increase in the levels of cyclin D1 transcripts, protein, and promoter activity. The results of these studies indicate that gastrin appears to exert its mitogenic effects on gastric adenocarcinoma, at least in part, through changes in cyclin D1 expression.
authors.affiliation: Section of Gastroenterology, Boston University School of Medicine, Boston Medical Center, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Diane H
authors.initials: DH
authors.lastname: Song
authors.forename: Basabi
authors.initials: B
authors.lastname: Rana
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Wolfe
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Crimmins
authors.forename: Caroline
authors.initials: C
authors.lastname: Choi
authors.forename: Chris
authors.initials: C
authors.lastname: Albanese
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: Richard G
authors.initials: RG
authors.lastname: Pestell
authors.forename: M Michael
authors.initials: MM
authors.lastname: Wolfe
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005755:Gastrins / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D005755:Gastrins; D006728:Hormones; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; C013550:gastrin 17