Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and proliferation in lung cancer.
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.
Volm
M
M
Department of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany.
Koomägi
R
R
D017209:Apoptosis / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology*; D011379:Prognosis; D016019:Survival Analysis; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors