Nuclear expression of hypoxia-inducible factor 1α protein is heterogeneous in human malignant cells under normoxic conditions

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor composed of α and β subunits, which plays an essential role in cancer cell hypoxia adaptation, glycolysis, and angiogenesis. Normally, HIF-1α protein, the dominant subunit of HIF-1, is accumulated in nuclei when cells are exposed to hypoxia (1% O₂) and rapidly degraded when cells are re-oxygenated. Here, we found that constitutive nuclear expression of HIF-1α protein was a general phenomenon in vitro under normoxic conditions in human malignant cells including those derived from the hematopoietic system, such as lymphoma and leukemia cells. In addition, the constitutive expression and induction of HIF-1α protein were more heterogeneous and dynamic compared with other transcription factors tested. HIF-2α and HIF-1β proteins showed a limited range of varieties among different cell lines and different extracellular stimuli. Mechanisms involved in sustaining constitutive expression of HIF-1α protein in malignant cells at normal oxygen tension warrant further investigation.