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

Hua Zhong, Angelo Michael Demarzo, 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

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Hypoxia-Inducible Factor 1
Neoplasm Metastasis
Neoplasms
Breast Neoplasms
Prostate
Colon
Breast
Immunohistochemistry
Brain Hypoxia
Facilitative Glucose Transport Proteins
Glycolysis
Brain Neoplasms
Vascular Endothelial Growth Factor A
Uterus
Stomach
Cell Proliferation
Carcinoma
Kidney
Lung
Skin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhong, H., Demarzo, A. M., Laughner, E., Lim, M., Hilton, D. A., Zagzag, D., ... Simons, J. W. (1999). Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. Cancer Research, 59(22), 5830-5835.

Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. / Zhong, Hua; Demarzo, Angelo Michael; Laughner, Erik; Lim, Michael; Hilton, David A.; Zagzag, David; Buechler, Peter; Isaacs, William B; Semenza, Gregg L; Simons, Jonathan W.

In: Cancer Research, Vol. 59, No. 22, 15.11.1999, p. 5830-5835.

Research output: Contribution to journalArticle

Zhong, H, Demarzo, AM, Laughner, E, Lim, M, Hilton, DA, Zagzag, D, Buechler, P, Isaacs, WB, Semenza, GL & Simons, JW 1999, 'Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases', Cancer Research, vol. 59, no. 22, pp. 5830-5835.
Zhong, Hua ; Demarzo, Angelo Michael ; Laughner, Erik ; Lim, Michael ; Hilton, David A. ; Zagzag, David ; Buechler, Peter ; Isaacs, William B ; Semenza, Gregg L ; Simons, Jonathan W. / Overexpression of hypoxia-inducible factor 1α in common human cancers and their metastases. In: Cancer Research. 1999 ; Vol. 59, No. 22. pp. 5830-5835.
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