Abstract
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates genes involved in adaptation to hypoxia. Expression of HIF-1α was evaluated in rat and human prostate cancer cell lines. Increased expression of HIF-1α mRNA in rat prostate cancer cell lines and hypoxia-induced expression of HIF-1α protein in human prostate cancer cell lines are associated with increased cell growth rates and metastatic potential. HIF-1α mRNA was undetectable in the normal rat ventral prostate by Northern blot hybridization. HIF-1α 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-1α expression than cells plated at high density independent of O2 tension. HIF-1α 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-1α protein under normoxic conditions.
Footnotes
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↵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.
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↵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 September 16, 1998.
- Accepted October 16, 1998.
- ©1998 American Association for Cancer Research.
Volume 58, Issue 23
