Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas

• Published in: International journal of cancer Vol. 103; no. 2; pp. 185 - 193
• Main Authors: Violette, Sabine, Festor, Estelle, Pandrea‐Vasile, Ivona, Mitchell, Valérie, Adida, Colette, Dussaulx, Elisabeth, Lacorte, Jean‐Marc, Chambaz, Jean, Lacasa, Michel, Lesuffleur, Thécla
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 10-01-2003; Wiley-Liss
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Antineoplastic agents; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Northern; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; cell survival; colon cancer cells; colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Drug Resistance, Neoplasm; drug‐resistance; Female; Fluorouracil - pharmacology; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; General aspects; HT29 Cells; Humans; Immunoenzyme Techniques; In Situ Hybridization; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Lithostathine; Male; Medical sciences; Multigene Family; Neoplasm Staging; Nerve Tissue Proteins; Pancreatitis-Associated Proteins; Pharmacology. Drug treatments; Reg IV; Reverse Transcriptase Polymerase Chain Reaction; RNA Probes; RNA, Messenger - metabolism; RNA, Neoplasm; Tumor Cells, Cultured; Adenocarcinoma; Antineoplastic agent; Human; Treatment resistance; Rectal disease; Gene overexpression; Malignant tumor; Colonic disease; Established cell line; Rectum; Digestive diseases; Genetics; Intestinal disease; Colon
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.10788

A better understanding of the mechanisms by which colon tumor cells are able to survive exposure to drugs would be valuable for the development of new therapeutic strategies. We used differential display‐PCR to compare gene expression in the drug‐sensitive HT‐29 colon cancer cell line and 3 drug‐resistant subpopulations derived from this parental cell line. One of the genes identified is a new gene, Regenerating IV gene (Reg IV), and was strongly overexpressed in HT‐29 drug‐resistant cells. Other drug‐resistant cell lines expressed Reg IV at a high level, whereas a low expression was noted in sensitive cell lines. Northern blot and real‐time PCR analysis showed that Reg IV is more strongly expressed in 71% of colorectal tumors (in particular in mucinous carcinomas) than in normal colon tissues. The comparison of Reg IV expression with that of other REG genes, Regenerating Iα or (Reg Iα), Regenerating Iβ (Reg Iβ) and Pancreatitis‐associated protein (PAP), highlights its predominant expression in colorectal tumors. Reg IV mRNA‐positive tumor cells display different phenotypes: mucus‐secreting, enterocyte‐like or undifferentiated. Interestingly, whereas Reg IV expression is low in normal colon, its level in normal small intestine is similar to that in some colorectal tumors. In normal tissue, Reg IV mRNA‐positive cells are mostly enteroendocrine cells and goblet cells. Our results point out the potential role of Reg IV in colorectal tumors and its subsequent interest as a pronostic indicator of tumor survival. © 2002 Wiley‐Liss, Inc.