Relevance of apoptosis and tolerance to hypoxic stress in cells transfected with receptor for advanced glycation end products (RAGE)

Anticancer Res. 2009 Apr;29(4):1287-94.

Abstract

Background: It has previously been reported that RAGE plays a role in resisting hypoxia in cancer cells. Here the mechanism of resistance of RAGE-transfected Cos7 cells to hypoxia is investigated from the standpoint of apoptosis.

Materials and methods: RAGE-transfected and mock-transfected Cos7 cells were subjected to hypoxia for 12, 24 and 36 h in an MTT assay. The expression of the apoptosis-regulatory proteins, hypoxia inducible factor-1(HIF-1a) and p53 in them was assessed by Western blotting.

Results: RAGE-transfected Cos7 cells showed better survival than mock-transfected Cos7 cells during hypoxia. The expression of many apoptosis-regulatory proteins was not affected. However, the expression of HIF-1a and p53 was weaker in RAGE-transfected Cos7 cells than in mock-transfected Cos7 cells.

Conclusion: The presence of RAGE might suppress HIF-1a protein expression, which in turn might induce an anti-apoptosis effect in RAGE-transfected Cos7 cells. Moreover, the p53 suppression induced by HIF-1a may lead to malignant potential in RAGE-transfected Cos7 cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Blotting, Western
  • COS Cells / metabolism
  • Chlorocebus aethiops
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism*
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-X Protein / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptor for Advanced Glycation End Products
  • Tumor Suppressor Protein p53
  • bcl-X Protein