Hypoxia-induced changes in the expression of VEGF, HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells

Anticancer Res. 2002 Sep-Oct;22(5):2697-702.

Abstract

Background: Hypoxia is important in cancer progression, and at the stage of detachment of the cancer cells from the primary lesion. This study was undertaken to analyze the effect of hypoxia on angiogenesis and cell proliferation in ovarian cancer.

Materials and methods: We first used immunohistochemistry to examine the expression of VEGF in 42 cases of ovarian carcinoma, with relevance to the p53 expression. Then, the expression of VEGF, HIF-1 alpha, cell cycle-related molecules and cell numbers were examined in 4 ovarian cancer cell lines with various p53 gene status.

Results: Immunohistochemistry showed that there was no significant correlation between VEGF and p53 expression. Moreover, hypoxia increased the expression of VEGF via up-regulation of HIF-1 alpha irrespective of p53 gene status. However hypoxia did not change the cell numbers, but influenced the expression of cell cycle-related molecules (increased p27 and decreased cyclin D1 and Rb).

Conclusion: Hypoxia increased VEGF expression in ovarian cancer cells irrespective of p53 gene status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / biosynthesis*
  • Cell Division / physiology
  • Cell Hypoxia / physiology
  • DNA-Binding Proteins / biosynthesis*
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Lymphokines / biosynthesis*
  • Lymphokines / genetics
  • Lymphokines / metabolism
  • Neovascularization, Pathologic / metabolism
  • Nuclear Proteins / biosynthesis*
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcription Factors*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Endothelial Growth Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors