title: Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric cancer.
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 5'-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 in the 5'-flanking region of the REG4 gene. Chromatin immunoprecipitation assays showed that CDX2 binds directly to the 5'-flanking region of REG4. These results indicate that CDX2 protein directly regulates Reg IV expression.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Takao
authors.initials: T
authors.lastname: Hinoi
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000071616:CDX2 Transcription Factor; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C428528:REG4 protein, human; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases