Tumor hypoxia and the progression of prostate cancer.
Tumor cell hypoxia is an innate environmental factor encountered during the development of many types of human tumors, including malignant prostate tumors. For prostate cancer, however, tumor cell hypoxia may be an even more critical element in tumor development and progression. Recent evidence suggests that androgenic steroids are important regulators of blood flow to prostate tumors and suppressors of tumor cell hypoxia. In addition, because prostate tumor cells are similar to other eukaryotic cells, they have the ability to respond to hypoxic conditions with drastic changes in gene expression mediated by the upregulation of a unique transcription factor, hypoxia-inducible factor-1. This response increases cancer cells' metabolic resistance to hypoxia, and also enhances the ability of prostate cancer cells to attract a more vigorous blood supply by upregulating the expression of pro-angiogenic factors. Because such changes would, in essence, increase the potential aggressiveness of affected prostate cancer cells, it is clear that tumor hypoxia has the potential for being a very important factor in prostate cancer cell biology. This review focuses on recent studies regarding the occurrence and potential role of hypoxia in prostate cancer, including hypoxia-inducible factor-1 and its related signaling pathways.
Anastasiadis
Aristotelis G
AG
Department of Urology, Columbia University, Herbert Irving Pavilion, 11th Floor, 161 Fort Washington Avenue, New York, NY 10032, USA.
Stisser
Brian C
BC
Ghafar
Mohamed A
MA
Burchardt
Martin
M
Buttyan
Ralph
R
D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000502:physiology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D009687:Nuclear Proteins / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases