reg iv is a direct target of intestinal transcriptional factor cdx2 in gastric cancerreg iv是肠道的直接目标转录因子cdx2在胃癌.pdfVIP

Reg IV Is a Direct Target of Intestinal Transcriptional Factor CDX2 in Gastric Cancer 1 1 2 1 1 2 Yutaka Naito , Naohide Oue , Takao Hinoi , Naoya Sakamoto , Kazuhiro Sentani , Hideki Ohdan , 3 3 1 Kazuyoshi Yanagihara , Hiroki Sasaki , Wataru Yasui * 1 Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan, 2 Department of Surgery, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan, 3 Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan Abstract REG4, which encodes Reg IV protein, is a member of the calcium-dependent lectin superfamily and potent activator of the epidermal growth factor receptor/Akt/activator protein-1 signaling pathway. Several human cancers overexpress Reg IV, and Reg IV expression is associated with intestinal phenotype differentiation. However, regulation of REG4 transcription remains unclear. In the present study, we investigated whether CDX2 regulates Reg IV expression in gastric cancer (GC) cells. Expression of Reg IV and CDX2 was analyzed by Western blot and quantitative reverse transcription–polymerase chain reaction in 9 GC cell lines and 2 colon cancer cell lines. The function of the 59-flanking region of the REG4 gene was characterized by luciferase assay. In 9 GC cell lines, endogenous Reg IV and CDX2 expression were well correlated. Using an estrogen receptor-regulated form of CDX2, rapid induction of Reg IV expression was observed in HT-29 cells. Reporter gene assays revealed an important role in transcription for consensus CDX2 DNA binding elements