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. 1999 Nov 15;59(22):5830-5.

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

H Zhong  1 , A M De Marzo, E Laughner, M Lim, D A Hilton, D Zagzag, P Buechler, W B Isaacs, G L Semenza, J W Simons
Affiliations
  • PMID: 10582706

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

H Zhong et al. Cancer Res. .

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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Comment in

  • Hypoxia-Inducible Factors in Cancer.
    Kim LC, Simon MC. Kim LC, et al. Cancer Res. 2022 Jan 15;82(2):195-196. doi: 10.1158/0008-5472.CAN-21-3780. Cancer Res. 2022. PMID: 35042744 Free PMC article.

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