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

Hua Zhong, Angelo M. De Marzo, Erik Laughner, Michael Lim, David A. Hilton, David Zagzag, Peter Buechler, William B. Isaacs, Gregg L. Semenza, Jonathan W. Simons

Research output: Contribution to journalArticle

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-1α subunit. In this study, HIF-1α expression was analyzed by immunohistochemistry in 179 tumor specimens. HIF- 1α 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-1α expression was correlated with aberrant p53 accumulation and cell proliferation. Preneoplastic lesions in breast, colon, and prostate overexpressed HIF-1α, whereas benign tumors in breast and uterus did not. HIF-1α overexpression was detected in only 29% of primary breast cancers but in 69% of breast cancer metastases. In brain tumors, HIF-1α immunohistochemistry demarcated areas of angiogenesis. These results provide the first clinical data indicating that HIF-1α may play an important role in human cancer progression.

Original languageEnglish (US)
Pages (from-to)5830-5835
Number of pages6
JournalCancer Research
Volume59
Issue number22
StatePublished - Nov 15 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases'. Together they form a unique fingerprint.

  • Cite this

    Zhong, H., De Marzo, A. M., Laughner, E., Lim, M., Hilton, D. A., Zagzag, D., Buechler, P., Isaacs, W. B., Semenza, G. L., & Simons, J. W. (1999). Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Research, 59(22), 5830-5835.