Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer.
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.
Zhong
H
H
James Buchanan Brady Urological Institute Research Laboratories, Johns Hopkins Hospital, Baltimore, Maryland 21287-2411, USA.
Agani
F
F
Baccala
A A
AA
Laughner
E
E
Rioseco-Camacho
N
N
Isaacs
W B
WB
Simons
J W
JW
Semenza
G L
GL
D000818:Animals; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D018450:Disease Progression; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors