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

J. Biol. Chem., Vol. 280, Issue 9, 7962-7975, March 4, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/9/7962    most recent M412593200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bommer, G. T. Articles by Kolligs, F. T. Search for Related Content PubMed PubMed Citation Articles by Bommer, G. T. Articles by Kolligs, F. T. Social Bookmarking                      What's this?

DRO1, a Gene Down-regulated by Oncogenes, Mediates Growth Inhibition in Colon and Pancreatic Cancer Cells^*

Guido T. Bommer, Claudia Jäger, Eva-Maria Dürr, Sebastian Baehs, Sören T. Eichhorst, Thomas Brabletz, Gang Hu¶||, Thomas Fröhlich**, Georg Arnold**, Dagmar C. Kress, Burkhard Göke, Eric R. Fearon¶, and Frank T. Kolligs

From the Department of Medicine II, University of Munich, 81377 Munich, Germany, the Institute of Pathology, University of Erlangen, 91054 Erlangen, Erlangen, Germany, the ^¶Division of Molecular Medicine & Genetics and the Cancer Center, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, the ^**Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, University of Munich, 81377 Munich, Germany, and the Institute of Molecular Animal Breeding and Biotechnology, University of Munich, 81377 Munich, Germany

Neoplastic progression in human tissues appears to be paralleled by a series of genetic and epigenetic alterations. In human colorectal cancers, defect Wnt/-catenin/T-cell factor and RAS/RAF signaling pathways have a major contributing role in tumor initiation and progression. To date, much of the research on the consequences of -catenin activation has been focused on genes whose expression is believed to be activated by -catenin-associated T-cell factor-dependent transcription. Little is known about genes whose expression may be down-regulated secondary to -catenin activation. Using a subtractive suppression hybridization approach, we identified a gene with markedly decreased expression in rat RK3E epithelial cells neoplastically transformed by -catenin. Because expression of this gene was also down-regulated in RK3E transformed by several other oncogenes, the gene was named DRO1 for "down-regulated by oncogenes 1." Compared with corresponding normal tissues, DRO1 expression was found to be very reduced in colon and pancreatic cancer cell lines as well as in most colorectal cancer specimens. The predicted DRO1 protein contains three repetitive elements with significant similarity to the carboxyl-terminal regions of the predicted proteins from DRS/SRPX/ETX1 and SRPUL genes, suggesting the existence of a new protein family. Ectopic expression of DRO1 in neoplastically transformed RK3E or colorectal and pancreatic cancer cell lines lacking endogenous DRO1 expression resulted in substantial inhibition of growth properties. DRO1 was found to suppress anchorage independent growth and to sensitize cells to anoikis and CD95-induced apoptosis. Our findings suggest that inhibition of DRO1 expression may be an important event in the development of colorectal and pancreatic cancers.

Received for publication, November 8, 2004

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY548105, AY548106, AY548107.

^* This work was supported by Deutsche Forschungsgemeinschaft Grants KO 1826/2-1 and KO 1826/2-3 and a FöFoLe grant from the Faculty of Medicine of the University of Munich. 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.

^|| Present address: Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, MI 48105.

To whom correspondence should be addressed: Dept. of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. E-mail: fkolligs{at}med.uni-muenchen.de.

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

This article has been cited by other articles:

				Y. Tambe, A. Yoshioka-Yamashita, K.-i. Mukaisho, S. Haraguchi, T. Chano, T. Isono, T. Kawai, Y. Suzuki, R. Kushima, T. Hattori, et al. Tumor prone phenotype of mice deficient in a novel apoptosis-inducing gene, drs Carcinogenesis, April 1, 2007; 28(4): 777 - 784. [Abstract] [Full Text] [PDF]