Reduced expression of DNA repair and redox signaling protein APE1/Ref-1 impairs human pancreatic cancer cell survival, proliferation, and cell cycle progression

Cancer Invest. 2010 Nov;28(9):885-95. doi: 10.3109/07357907.2010.512816.

Abstract

Pancreatic cancer is a deadly disease that is virtually never cured. Understanding the chemoresistance intrinsic to this cancer will aid in developing new regimens. High expression of APE1/Ref-1, a DNA repair and redox signaling protein, is associated with resistance, poor outcome, and angiogenesis; little is known in pancreatic cancer. Immunostaining of adenocarcinoma shows greater APE1/Ref-1 expression than in normal pancreas tissue. A decrease in APE1/Ref-1 protein levels results in pancreatic cancer cell growth inhibition, increased apoptosis, and altered cell cycle progression. Endogenous cell cycle inhibitors increase when APE1/ Ref-1 is reduced, demonstrating its importance to proliferation and growth of pancreatic cancer.

MeSH terms

  • Blotting, Western
  • Cell Cycle*
  • Cell Division
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation*
  • Cell Survival
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Repair
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • G2 Phase
  • Humans
  • Immunohistochemistry
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • RNA Interference
  • Reactive Oxygen Species / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • Reactive Oxygen Species
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase