title: Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: a novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin.
abstract: Somatostatin (SST) is a regulatory peptide and acts as an endogenous inhibitory regulator of the secretory and proliferative responses of target cells. SST's actions are mediated by a family of seven transmembrane domain G protein-coupled receptors that comprise five distinct subtypes (SSTR1-5). SSTR5 is one of the major SSTRs in the islets of Langerhans. Homeodomain-containing transcription factor pancreatic and duodenal homeobox-1 (PDX-1) is essential for pancreatic development, β cell differentiation, maintenance of normal β cell functions in adults and tumorigenesis. Recent studies show that SSTR5 acts as a negative regulator for PDX-1 expression and that SSTR5 mediates somatostatin's inhibitory effect on cell proliferation and insulin expression/excretion through down-regulating PDX-1 expression. SSTR5 exerts its inhibitory effect on PDX-1 expression at both the transcriptional level by down-regulating PDX-1 mRNA and the post-translational level by enhancing PDX-1 ubiquitination. Identification of PDX-1 as a transcriptional target for SSTR5 may help in guiding the choice of therapeutic cancer treatments.
authors.affiliation: Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Zhou
authors.affiliation: CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Sinnett-Smith
authors.affiliation: Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: Shi-He
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: Juehua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: Robbi
authors.initials: R
authors.lastname: Sanchez
authors.affiliation: CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; Department of Medicine at Cedars Sinai Medical Center Los Angeles, CA, USA ; Veterans Affairs Los Angeles, CA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Pandol
authors.affiliation: Materials and Process Simulation Center, California Institute of Technology Pasadena, CA, USA.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Abrol
authors.affiliation: Gradalis, Inc., Dallas, TX, USA ; Mary Crowley Cancer Research Centers Dallas, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.affiliation: CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Rozengurt
authors.affiliation: Division of General Surgery, Department of Surgery, David Geffen School of Medicine at University of California Los Angeles, CA, USA ; CURE: Digestive Disease Research Center, David Geffen School of Medicine at University of California Los Angeles, CA, USA.
authors.forename: F Charles
authors.initials: FC
authors.lastname: Brunicardi
keywords: G protein-coupled receptors; pancreatic and duodenal homeobox-1; single nucleotide polymorphisms; somatostatin; somatostatin receptor