Elevated DNA polymerase iota (Poli) is involved in the acquisition of aggressive phenotypes of human esophageal squamous cell cancer

Int J Clin Exp Pathol. 2015 Apr 1;8(4):3591-601. eCollection 2015.

Abstract

DNA polymerase iota (Polι) can repair several types of DNA damage but has extremely low fidelity. Previous studies have shown an aberrantly elevated Polι expression in human esophageal squamous cell cancer tissues. However, there were few reports describing the role of Polι in esophageal cancer progression. Based on Real-time PCR assay, we found Polι expression was up-regulated in esophageal cancer tissues compared to adjacent normal tissues and overexpression of Polι was correlated to lymph node metastasis. Clonogenic assay and transwell chamber assay showed that overexpression of Polι had higher clongenic capability and invasive tendency in human esophageal squamous cell cancer cells. Expression of cyclin D1, an important cell cycle regulator, was found to be associated with that of Polι in tissue samples and cancer cells as analyzed by real-time PCR, immunohistochemistry, Western blotting and immunofluorescence assay. Flow cytometry analysis further showed that cell cycle distribution was altered in Polι overexpressing cells. These results indicated that expression of Polι correlates significantly with tumor proliferation and invasion. We conclude that Polι is involved in the degree of aggressiveness of human esophageal squamous cell cancer.

Keywords: DNA polymerase iota; Esophageal cancer; cyclin D1; metastasis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Damage
  • DNA Polymerase iota
  • DNA-Directed DNA Polymerase / genetics*
  • DNA-Directed DNA Polymerase / metabolism
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Phenotype
  • Up-Regulation

Substances

  • DNA-Directed DNA Polymerase
  • DNA Polymerase iota
  • POLI protein, human