Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and proliferation in lung cancer

Anticancer Res. 2000 May-Jun;20(3A):1527-33.


Hypoxia-inducible factor 1 (HIF-1) plays an important role in the pleiotropic response observed under hypoxia. In this study we examined whether a relationship exists between HIF-1 proteins and proliferation and apoptosis in lung cancer. To this purpose, we used immunohistochemistry to analyze HIF-1 alpha and HIF-1 beta in formalin-fixed, paraffin-embedded, non-small cell lung carcinomas (n = 96) and compared the HIF expression with cyclin A protein expression, cell cycle phases, the apoptotic index and the expression of caspase 3, Fas and Fas ligand. Additionally, we examined whether HIF-1 determinations can improve the prognostic information concerning a patient's overall survival. A relationship between HIF-1 alpha or HIF-1 beta and proliferation could not be observed. However, a significant correlation between HIF-1 expression, apoptosis and the pro-apoptotic factors caspase-3, Fas, and Fas ligand could be detected. Patients with HIF-positive carcinomas had significantly longer median survival times than patients with HIF-negative carcinomas (HIF-1 alpha: 191 vs. 60 weeks; P = 0.05; HIF-1 beta: 111 vs. 41 weeks; P = 0.003). Multivariate analyses demonstrated that the presence of HIF-1 at a given stage or extent of lymph node involvement is an independent prognostic factor for the survival of patients with non-small cell lung carcinomas.

MeSH terms

  • Apoptosis / physiology*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Division / physiology
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / physiology*
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunohistochemistry
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Middle Aged
  • Nuclear Proteins / analysis
  • Nuclear Proteins / physiology*
  • Prognosis
  • Survival Analysis
  • Transcription Factors*
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Transcription Factors