Abstract
The regenerating islet-derived members (Reg), a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerating islet-derived type IV (RegIV), a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogenesis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that without such expression, and RegIV is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegIV mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegIV gene expression was a significant independent predictor of colorectal cancer. The biologic functions of RegIV protein in cancer tissue, associated with carcinogenesis, anti-apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strategies for gastroenterological cancers expressing RegIV. This review article summarizes the current information related to biological functions as well as clinical importance of RegIV gene to clarify the significance of RegIV expression in gastroenterological cancers.