HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Höcker, M. Articles by Wang, T. C. Search for Related Content PubMed PubMed Citation Articles by Höcker, M. Articles by Wang, T. C. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 51, 34000-34007, December 18, 1998

Sp1 and CREB Mediate Gastrin-dependent Regulation of Chromogranin A Promoter Activity in Gastric Carcinoma Cells

Michael Höcker, Raktima Raychowdhury^§, Thomas Plath^¶, Hongjang Wu, Daniel T. O'Connor, Bertram Wiedenmann, Stefan Rosewicz^¶, and Timothy C. Wang^§

From the  Medizinische Klink mit Schwerpunkt Gastroenterologie und Hepatologie, Universitätsklinikum Charitè, Campus Virchow-Klinikum, Humboldt Universität Berlin, Germany, the ^¶ Innere Medizin I, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany, the  Department of Medicine and Center for Molecular Genetics, University of California San Diego, San Diego, California 92161, and the ^§ Gastrointestinal Unit and Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Chromogranin A (CgA) is a multifunctional acidic protein that in the stomach is expressed predominantly in enterochromaffin-like cells (ECL cells) where it is regulated by gastrin. In order to investigate the transcriptional response of the mouse CgA (mCgA) promoter to gastrin stimulation, we studied a 4.8-kilobase mCgA promoter-luciferase reporter gene construct in transiently transfected AGS-B cells. 5'-Deletion analysis and scanning mutagenesis of mCgA 5'-flanking DNA showed that a Sp1/Egr-1 site spanning 88 to 77 base pairs (bp) and a cyclic AMP-responsive element (CRE) at 71 to 64 bp are essential for gastrin-dependent mCgA transactivation. Gastrin stimulation increased cellular Sp1 protein levels and Sp1-binding to the mCgA 88 to 77 bp element, as well as binding of CREB to its consensus motif at 71 to 64 bp. Gastrin also stimulated CREB Ser-133 phosphorylation, and abundance of cellular CREB protein levels. Overexpression of either Sp1 or phosphorylated CREB transactivated the mCgA promoter dose dependently, while coexpression of both transcription factors resulted in an additive mCgA promoter response. mCgA 92 to 64 bp, comprising the Sp1/Egr-1 site and the CRE motif, conferred gastrin responsiveness to a heterologous thymidine kinase promoter system, and therefore functions as a "true" enhancer element. This report demonstrates that Sp1 and CREB mediate CCK-B/gastrin receptor-dependent gene regulation, and that the effect of gastrin on the CgA gene is brought about by cooperative action of both transcription factors.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Almeida-Vega, K. Catlow, S. Kenny, R. Dimaline, and A. Varro Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1 Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G414 - G423. [Abstract] [Full Text] [PDF]

				D. Chinnappan, X. Qu, D. Xiao, A. Ratnasari, and H. C. Weber Human gastrin-releasing peptide receptor gene regulation requires transcription factor binding at two distinct CRE sites Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G153 - G162. [Abstract] [Full Text] [PDF]

				K. Catlow, H. L. Ashurst, A. Varro, and R. Dimaline Identification of a Gastrin Response Element in the Vesicular Monoamine Transporter Type 2 Promoter and Requirement of 20 S Proteasome Subunits for Transcriptional Activity J. Biol. Chem., June 8, 2007; 282(23): 17069 - 17077. [Abstract] [Full Text] [PDF]

				S. Tu, A. L. Chi, S. Lim, G. Cui, Z. Dubeykovskaya, W. Ai, J. V. Fleming, S. Takaishi, and T. C. Wang Gastrin regulates the TFF2 promoter through gastrin-responsive cis-acting elements and multiple signaling pathways Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1726 - G1737. [Abstract] [Full Text] [PDF]

				R. N. Jain and L. C. Samuelson Transcriptional profiling of gastrin-regulated genes in mouse stomach Physiol Genomics, March 14, 2007; 29(1): 1 - 12. [Abstract] [Full Text] [PDF]

				W. Ai, Y. Liu, and T. C. Wang Yin yang 1 (YY1) represses histidine decarboxylase gene expression with SREBP-1a in part through an upstream Sp1 site Am J Physiol Gastrointest Liver Physiol, June 1, 2006; 290(6): G1096 - G1104. [Abstract] [Full Text] [PDF]

				R. N. Jain, C. S. Brunkan, C. S. Chew, and L. C. Samuelson Gene expression profiling of gastrin target genes in parietal cells Physiol Genomics, January 12, 2006; 24(2): 124 - 132. [Abstract] [Full Text] [PDF]

				K. Matlhagela, M. Borsick, T. Rajkhowa, and M. Taub Identification of a Prostaglandin-responsive Element in the Na,K-ATPase {beta}1 Promoter That Is Regulated by cAMP and Ca2+: EVIDENCE FOR AN INTERACTIVE ROLE OF cAMP REGULATORY ELEMENT-BINDING PROTEIN AND Sp1 J. Biol. Chem., January 7, 2005; 280(1): 334 - 346. [Abstract] [Full Text] [PDF]

				N. F. Sinclair, W. Ai, R. Raychowdhury, M. Bi, T. C. Wang, T. J. Koh, and J. T. McLaughlin Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism Am J Physiol Gastrointest Liver Physiol, June 1, 2004; 286(6): G992 - G999. [Abstract] [Full Text] [PDF]

				W. Ai, Y. Liu, M. Langlois, and T. C. Wang Kruppel-like Factor 4 (KLF4) Represses Histidine Decarboxylase Gene Expression through an Upstream Sp1 Site and Downstream Gastrin Responsive Elements J. Biol. Chem., March 5, 2004; 279(10): 8684 - 8693. [Abstract] [Full Text] [PDF]

				D. H. Song, B. Rana, J. R. Wolfe, G. Crimmins, C. Choi, C. Albanese, T. C. Wang, R. G. Pestell, and M. M. Wolfe Gastrin-induced gastric adenocarcinoma growth is mediated through cyclin D1 Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G217 - G222. [Abstract] [Full Text] [PDF]

				M. Gerhard, N. Neumayer, E. Presecan-Siedel, R. Zanner, E. Lengyel, T. Cramer, M. Hocker, and C. Prinz Gastrin Induces Expression and Promoter Activity of the Vesicular Monoamine Transporter Subtype 2 Endocrinology, August 1, 2001; 142(8): 3663 - 3672. [Abstract] [Full Text] [PDF]

				G J Dockray Gastrin and gastric epithelial physiology J. Physiol., July 15, 1999; 518(2): 315 - 324. [Abstract] [Full Text] [PDF]

				F. Watson, R. S. Kiernan, D. G. Deavall, A. Varro, and R. Dimaline Transcriptional Activation of the Rat Vesicular Monoamine Transporter 2 Promoter in Gastric Epithelial Cells. REGULATION BY GASTRIN J. Biol. Chem., March 2, 2001; 276(10): 7661 - 7671. [Abstract] [Full Text] [PDF]