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Research Paper
Dysregulation of Reg Gene Expression Occurs Early in Gastrointestinal Tumorigenesis and Regulates Anti-Apoptotic Genes
Kumar S Bishnupuri, Qizhi Luo, Joshua R Korzenik, Jeffrey O Henderson, Courtney W Houchen, Shrikant Anant and Brian K Dieckgraefe
volume 5 | issue 12
december 2006Pages: 1714 - 1720
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Expression of anti-apoptotic genes is frequently elevated in tumors, where they increase resistance to chemotherapeutic agents and predict poor patient outcomes. However, key cellular factors regulating anti-apoptotic genes in tumors remain unknown. Increased expression of the regenerating (Reg) genes is commonly observed in gastrointestinal (GI) malignancies including colorectal cancer (CRC). We therefore examined Reg gene expression and associated changes in anti-apoptotic genes in an animal model of GI tumorigenesis. Using real time RT-PCR, we measured expression of Reg genes in human colorectal adenocarcinoma specimens, colon adenocarcinoma cell lines and adenomas from multiple intestinal neoplasia (min) mice heterozygous for a germ-line mutation of the adenomatous polyposis coli (APC) gene. Expression of Reg genes is increased in human colorectal adenocarcinomas and in the intestine of APCmin/+ mice at 4 weeks of age, a time preceding the spontaneous second mutation in the APC gene. Individual Reg genes exhibited regional expression profiles across the GI tract in mice. Adenomas from 14-week old mice had significant increases in at least one member of the Reg gene family, most commonly Reg IV and an associated increase in expression of the anti-apoptotic gene, Bcl-2. Addition of exogenous recombinant human Reg IV to human colon adenocarcinoma cells significantly increased Bcl-2 and Bcl-xL expression and induced resistance to ionizing radiation. These results show that dysregulation of Reg genes occur early in tumorigenesis. Furthermore, increased expression of Reg genes, specifically Reg IV contribute to adenoma formation and lead to increased resistance to apoptotic cell death in CRC.
Authors
Kumar S Bishnupuri
Washington University School of Medicine, St. Louis, MO
Qizhi Luo
Washington University School of Medicine, St. Louis, MO
Joshua R Korzenik
Massachusetts General Hospital, Boston, Massachusetts
Jeffrey O Henderson
Tabor College, Hillsboro Kansas
Courtney W Houchen
University of Oklahoma Health Sciences Center, Oklahoma City, OK
Shrikant Anant
University of Oklahomlth Sciences Center, Oklahoma City, Oa HeaK
Brian K Dieckgraefe
Washington University School of Medicine, St. Louis, MO
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.