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

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor composed of alpha and beta subunits, which plays an essential role in cancer cell hypoxia adaptation, glycolysis, and angiogenesis. Normally, HIF-1alpha 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-1alpha 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-1alpha protein were more heterogeneous and dynamic compared with other transcription factors tested. HIF-2alpha and HIF-1beta proteins showed a limited range of varieties among different cell lines and different extracellular stimuli. Mechanisms involved in sustaining constitutive expression of HIF-1alpha protein in malignant cells at normal oxygen tension warrant further investigation.