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Increased Expression of Hypoxia Inducible Factor-1 in Rat and Human Prostate Cancer¹

James Buchanan Brady Urological Institute Research Laboratories [H. Z., A. A. B., N. R.-C., W. B. I., J. W. S.], the Center for Medical Genetics [G. L. S.], Department of Pediatrics and Medicine [F. A., E. L., G. L. S.], and Oncology Center [H. Z., J. W. S.], Johns Hopkins Hospital, Baltimore, Maryland 21287-2411

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates genes involved in adaptation to hypoxia. Expression of HIF-1 was evaluated in rat and human prostate cancer cell lines. Increased expression of HIF-1 mRNA in rat prostate cancer cell lines and hypoxia-induced expression of HIF-1 protein in human prostate cancer cell lines are associated with increased cell growth rates and metastatic potential. HIF-1 mRNA was undetectable in the normal rat ventral prostate by Northern blot hybridization. HIF-1 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-1 expression than cells plated at high density independent of O₂ tension. HIF-1 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-1 protein under normoxic conditions.

¹ This work was supported by Prostate Cancer SPORE Grant CA-58236 from the NIH, a grant from the CaPCure Foundation, and Prostate Cancer Grant DAMD 17-98-1-8475 from the Department of Defense.

² To whom requests for reprints should be addressed, at James Buchanan Brady Urological Institute, Marburg 409, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287-2411.

Received 9/16/98. Accepted 10/16/98.

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