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Reg IV is a direct target of intestinal transcriptional factor CDX2 in gastric cancer

Yutaka Naito1, Naohide Oue, Takao Hinoi

  • 1Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

Plos One
|November 8, 2012
PubMed

Insights

CDX2 protein directly regulates Reg IV expression in gastric cancer (GC) cells. This finding clarifies the transcriptional regulation of Reg IV, a protein implicated in several human cancers.

Area of Science:

  • Molecular biology
  • Cancer research
  • Gene regulation

Background:

  • Reg IV protein, encoded by REG4, is a calcium-dependent lectin superfamily member and activator of the EGFR/Akt/AP-1 pathway.
  • Reg IV overexpression is observed in several human cancers and linked to intestinal differentiation.
  • Mechanisms regulating REG4 transcription are not fully understood.

Purpose of the Study:

  • To investigate the role of CDX2 in regulating Reg IV expression in gastric cancer (GC) cells.
  • To elucidate the transcriptional control of REG4 by CDX2.

Main Methods:

  • Analysis of Reg IV and CDX2 expression in 9 GC and 2 colon cancer cell lines using Western blot and qRT-PCR.
  • Luciferase assays to characterize the function of the REG4 gene's 5'-flanking region.
  • Chromatin immunoprecipitation (ChIP) assays to assess CDX2 binding to the REG4 promoter.

Main Results:

  • Endogenous Reg IV and CDX2 expression levels were correlated in GC cell lines.
  • Inducible CDX2 expression led to rapid induction of Reg IV expression in HT-29 cells.
  • Reporter gene assays and ChIP assays confirmed direct binding of CDX2 to CDX2 DNA binding elements in the REG4 5'-flanking region.

Conclusions:

  • CDX2 directly regulates the transcription of the REG4 gene.
  • This study identifies CDX2 as a key transcriptional regulator of Reg IV in gastric cancer.

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