Increased Expression of Hypoxia Inducible Factor-1alpha in Rat and Human Prostate Cancer.
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Cancer research, Vol: 58, Issue: 23, Page: 5280-5284
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- Animals; DNA; Neoplasm; DNA-Binding Proteins; Disease Progression; Humans; Hypoxia-Inducible Factor 1; alpha Subunit; Male; Nuclear Proteins; Prostatic Neoplasms; RNA; Messenger; Rats; Transcription Factors; Tumor Cells; Cultured; Medicine and Health Sciences; Other Medical Specialties; Surgery; Urology
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates genes involved in adaptation to hypoxia. Expression of HIF-1alpha was evaluated in rat and human prostate cancer cell lines. Increased expression of HIF-1alpha mRNA in rat prostate cancer cell lines and hypoxia-induced expression of HIF-1alpha protein in human prostate cancer cell lines are associated with increased cell growth rates and metastatic potential. HIF-1alpha mRNA was undetectable in the normal rat ventral prostate by Northern blot hybridization. HIF-1alpha protein expression and HIF-1 DNA binding activity were detected in normoxic PC-3 cells. Human prostate cancer cells plated at low density manifested higher functional HIF-1alpha expression than cells plated at high density independent of O2 tension. HIF-1alpha may become dysregulated in prostate cancer and thus drive the transcription of hypoxia-adaptive genes involved in tumor progression. This is also the first evidence that human cancer cells can express functional HIF-1alpha protein under normoxic conditions.