Gastrin-induced gastric adenocarcinoma growth is mediated through cyclin D1.
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.
Song
Diane H
DH
Section of Gastroenterology, Boston University School of Medicine, Boston Medical Center, 650 Albany Street, Boston, MA 02118, USA.
Rana
Basabi
B
Wolfe
Jessica R
JR
Crimmins
Geoffrey
G
Choi
Caroline
C
Albanese
Chris
C
Wang
Timothy C
TC
Pestell
Richard G
RG
Wolfe
M Michael
MM
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
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