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

J. Biol. Chem., Vol. 279, Issue 33, 34397-34405, August 13, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/33/34397    most recent M314021200v1 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 Jette, C. Articles by Jones, D. A. Search for Related Content PubMed PubMed Citation Articles by Jette, C. Articles by Jones, D. A. Social Bookmarking                      What's this?

The Tumor Suppressor Adenomatous Polyposis Coli and Caudal Related Homeodomain Protein Regulate Expression of Retinol Dehydrogenase L^*

Cicely Jette, Peter W. Peterson, Imelda T. Sandoval¶, Elizabeth J. Manos, Eryn Hadley, Chris M. Ireland¶, and David A. Jones¶||

From the Huntsman Cancer Institute, Departments of Oncological Sciences and ^¶Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112

Development of normal colon epithelial cells proceeds through a systematic differentiation of cells that emerge from stem cells within the base of colon crypts. Genetic mutations in the adenomatous polyposis coli (APC) gene are thought to cause colon adenoma and carcinoma formation by enhancing colonocyte proliferation and impairing differentiation. We currently have a limited understanding of the cellular mechanisms that promote colonocyte differentiation. Herein, we present evidence supporting a lack of retinoic acid biosynthesis as a mechanism contributing to the development of colon adenomas and carcinomas. Microarray and reverse transcriptase-PCR analyses revealed reduced expression of two retinoid biosynthesis genes: retinol dehydrogenase 5 (RDH5) and retinol dehydrogenase L (RDHL) in colon adenomas and carcinomas as compared with normal colon. Consistent with the adenoma and carcinomas samples, seven colon carcinoma cell lines also lacked expression of RDH5 and RDHL. Assessment of RDH enzymatic activity within these seven cell lines showed poor conversion of retinol into retinoic acid when compared with normal cells such as normal human mammary epithelial cells. Reintroduction of wild type APC into an APC-deficient colon carcinoma cell line (HT29) resulted in increased expression of RDHL without affecting RDH5. APC-mediated induction of RDHL was paralleled by increased production of retinoic acid. Investigations into the mechanism responsible for APC induction of RDHL indicated that -catenin fails to repress RDHL. The colon-specific transcription factor CDX2, however, activated an RDHL promoter construct and induced endogenous RDHL. Finally, the induction of RDHL by APC appears dependent on the presence of CDX2. We propose a novel role for APC and CDX2 in controlling retinoic acid biosynthesis and in promoting a retinoid-induced program of colonocyte differentiation.

Received for publication, December 22, 2003 , and in revised form, June 2, 2004.

^* This work was supported by American Cancer Society Grant RSG02-141-01-CNE (to D. A. J.) and by National Institutes of Health Genetics Training Grant 5T32 GM07464 (to C. J.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Huntsman Cancer Institute, 2000 Circle of Hope, Rm. 5262, Salt Lake City, UT 84112. Tel.: 801-585-6107; Fax: 801-585-0900; E-mail: david.jones{at}hci.utah.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. L. Eisinger, L. D. Nadauld, D. N. Shelton, S. M. Prescott, D. M. Stafforini, and D. A. Jones Retinoic Acid Inhibits beta-Catenin through Suppression of Cox-2: A ROLE FOR TRUNCATED ADENOMATOUS POLYPOSIS COLI J. Biol. Chem., October 5, 2007; 282(40): 29394 - 29400. [Abstract] [Full Text] [PDF]

				L. Wang, Y. Tang, D. C. Rubin, and M. S. Levin Chronically administered retinoic acid has trophic effects in the rat small intestine and promotes adaptation in a resection model of short bowel syndrome Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1559 - G1569. [Abstract] [Full Text] [PDF]

				R. J. Jones, S. Dickerson, P. M. Bhende, H.-J. Delecluse, and S. C. Kenney Epstein-Barr Virus Lytic Infection Induces Retinoic Acid-responsive Genes through Induction of a Retinol-metabolizing Enzyme, DHRS9 J. Biol. Chem., March 16, 2007; 282(11): 8317 - 8324. [Abstract] [Full Text] [PDF]

				L. D. Nadauld, R. Phelps, B. C. Moore, A. Eisinger, I. T. Sandoval, S. Chidester, P. W. Peterson, E. J. Manos, B. Sklow, R. W. Burt, et al. Adenomatous Polyposis Coli Control of C-terminal Binding Protein-1 Stability Regulates Expression of Intestinal Retinol Dehydrogenases J. Biol. Chem., December 8, 2006; 281(49): 37828 - 37835. [Abstract] [Full Text] [PDF]

				I. Szatmari, A. Pap, R. Ruhl, J.-X. Ma, P. A. Illarionov, G. S. Besra, E. Rajnavolgyi, B. Dezso, and L. Nagy PPAR{gamma} controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells J. Exp. Med., October 2, 2006; 203(10): 2351 - 2362. [Abstract] [Full Text] [PDF]

				L. D. Nadauld, S. Chidester, D. N. Shelton, K. Rai, T. Broadbent, I. T. Sandoval, P. W. Peterson, E. J. Manos, C. M. Ireland, H. J. Yost, et al. Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development PNAS, September 5, 2006; 103(36): 13409 - 13414. [Abstract] [Full Text] [PDF]

				D. N. Shelton, I. T. Sandoval, A. Eisinger, S. Chidester, A. Ratnayake, C. M. Ireland, and D. A. Jones Up-regulation of CYP26A1 in Adenomatous Polyposis Coli-Deficient Vertebrates via a WNT-Dependent Mechanism: Implications for Intestinal Cell Differentiation and Colon Tumor Development. Cancer Res., August 1, 2006; 66(15): 7571 - 7577. [Abstract] [Full Text] [PDF]

				A. L. Eisinger, L. D. Nadauld, D. N. Shelton, P. W. Peterson, R. A. Phelps, S. Chidester, D. M. Stafforini, S. M. Prescott, and D. A. Jones The Adenomatous Polyposis Coli Tumor Suppressor Gene Regulates Expression of Cyclooxygenase-2 by a Mechanism That Involves Retinoic Acid J. Biol. Chem., July 21, 2006; 281(29): 20474 - 20482. [Abstract] [Full Text] [PDF]

				M. Liden and U. Eriksson Understanding Retinol Metabolism: Structure and Function of Retinol Dehydrogenases J. Biol. Chem., May 12, 2006; 281(19): 13001 - 13004. [Full Text] [PDF]

				E. Y. Park, A. Dillard, E. A. Williams, E. T. Wilder, M. R. Pepper, and M. A. Lane Retinol Inhibits the Growth of All-Trans-Retinoic Acid-Sensitive and All-Trans-Retinoic Acid-Resistant Colon Cancer Cells through a Retinoic Acid Receptor-Independent Mechanism Cancer Res., November 1, 2005; 65(21): 9923 - 9933. [Abstract] [Full Text] [PDF]

				L. D. Nadauld, D. N. Shelton, S. Chidester, H. J. Yost, and D. A. Jones The Zebrafish Retinol Dehydrogenase, rdh1l, Is Essential for Intestinal Development and Is Regulated by the Tumor Suppressor Adenomatous Polyposis Coli J. Biol. Chem., August 26, 2005; 280(34): 30490 - 30495. [Abstract] [Full Text] [PDF]

				L. D. Nadauld, I. T. Sandoval, S. Chidester, H. J. Yost, and D. A. Jones Adenomatous Polyposis Coli Control of Retinoic Acid Biosynthesis Is Critical for Zebrafish Intestinal Development and Differentiation J. Biol. Chem., December 3, 2004; 279(49): 51581 - 51589. [Abstract] [Full Text] [PDF]