title: Role of endogenous cholecystokinin on growth of human pancreatic cancer.
abstract: Cholecystokinin (CCK) and gastrin stimulate growth of pancreatic cancer. Although down-regulation of gastrin inhibits growth of pancreatic cancer, the contribution of endogenous CCK to tumor growth is unknown. The purpose of this study was to evaluate the role of endogenous CCK on autocrine growth of pancreatic cancer. Pancreatic cancer cell lines were analyzed for CCK mRNA and peptide expression by real-time RT-PCR and radioimmunoassay, respectively. The effect of endogenous CCK on growth was evaluated by treating cancer cells with CCK neutralizing antibodies and by down-regulating CCK mRNA by RNAi. Wild-type pancreatic cancer cells expressed significantly lower CCK mRNA and peptide levels than gastrin. Neither treatment of pancreatic cancer cells with CCK antibodies nor the down-regulation of CCK mRNA and peptide by shRNAs altered growth in vitro or in vivo. Conversely, when gastrin mRNA expression was down-regulated, the same cells failed to produce tumors in spite of having sustained levels of endogenous CCK. Pancreatic cancer cells produce CCK and gastrin; however, the autocrine production of gastrin is more important for stimulating tumor growth.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
authors.forename: Gail L
authors.initials: GL
authors.lastname: Matters
authors.forename: Christopher
authors.initials: C
authors.lastname: McGovern
authors.forename: John F
authors.initials: JF
authors.lastname: Harms
authors.forename: Kevin
authors.initials: K
authors.lastname: Markovic
authors.forename: Krystal
authors.initials: K
authors.lastname: Anson
authors.forename: Calpurnia
authors.initials: C
authors.lastname: Jayakumar
authors.forename: Melissa
authors.initials: M
authors.lastname: Martenis
authors.forename: Christina
authors.initials: C
authors.lastname: Awad
authors.forename: Jill P
authors.initials: JP
authors.lastname: Smith
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D019898:Autocrine Communication / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002766:Cholecystokinin / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005755:Gastrins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D057134:Antibodies, Neutralizing; D005755:Gastrins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002766:Cholecystokinin