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      Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases.

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          Abstract

          Neovascularization and increased glycolysis, two universal characteristics of solid tumors, represent adaptations to a hypoxic microenvironment that are correlated with tumor invasion, metastasis, and lethality. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. HIF-1 transcriptional activity is determined by regulated expression of the HIF-1alpha subunit. In this study, HIF-1alpha expression was analyzed by immunohistochemistry in 179 tumor specimens. HIF-1alpha was overexpressed in 13 of 19 tumor types compared with the respective normal tissues, including colon, breast, gastric, lung, skin, ovarian, pancreatic, prostate, and renal carcinomas. HIF-1alpha expression was correlated with aberrant p53 accumulation and cell proliferation. Preneoplastic lesions in breast, colon, and prostate overexpressed HIF-1alpha, whereas benign tumors in breast and uterus did not. HIF-1alpha overexpression was detected in only 29% of primary breast cancers but in 69% of breast cancer metastases. In brain tumors, HIF-1alpha immunohistochemistry demarcated areas of angiogenesis. These results provide the first clinical data indicating that HIF-1alpha may play an important role in human cancer progression.

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          Author and article information

          Journal
          Cancer Res
          Cancer research
          0008-5472
          0008-5472
          Nov 15 1999
          : 59
          : 22
          Affiliations
          [1 ] The Johns Hopkins Oncology Center, Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
          Article
          10582706
          d733cb8b-3bd5-4a4a-9cfa-c5d13ee37f7a
          History

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