Overexpression of DNA polymerase iota (Polι) in esophageal squamous cell carcinoma

Cancer Sci. 2012 Aug;103(8):1574-9. doi: 10.1111/j.1349-7006.2012.02309.x. Epub 2012 May 30.

Abstract

The present study investigated the transcriptional regulation of low-fidelity translesion DNA synthesis (TLS) polymerases in human esophageal carcinoma. Significantly higher mRNA expression of polymerase zeta (Polξ), RAD18, polymerase iota (Polι), and polymerase kappa (Polκ) was found in esophageal carcinomas. The increased expression of Polι in tumor samples was further confirmed by immunohistochemistry. The promoter of POLI that encodes Polι was found to be hypomethylated, although the overexpression of this gene was unlikely to be associated with methylation in tumors. We further identified Sp1 and Oct-1 binding sites present in the POLI promoter. We observed that the binding affinity of Sp1 to the POLI promoter was significantly increased in cancerous tissues and that Sp1 activated POLI gene transcription in cultured cell lines. The present study demonstrates overexpression of the TLS genes in esophageal carcinoma and identifies a key role for Sp1 in upregulating POLI gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • DNA Methylation
  • DNA-Directed DNA Polymerase / metabolism*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / metabolism*
  • Esophagus / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Molecular Sequence Data
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction

Substances

  • RNA, Messenger
  • DNA polymerase iota
  • DNA-Directed DNA Polymerase