PT  - JOURNAL ARTICLE
AU  - Zhong, Hua
AU  - De Marzo, Angelo M.
AU  - Laughner, Erik
AU  - Lim, Michael
AU  - Hilton, David A.
AU  - Zagzag, David
AU  - Buechler, Peter
AU  - Isaacs, William B.
AU  - Semenza, Gregg L.
AU  - Simons, Jonathan W.
TI  - Overexpression of Hypoxia-inducible Factor 1α in Common Human Cancers and Their Metastases
DP  - 1999 Nov 15
TA  - Cancer Research
PG  - 5830--5835
VI  - 59
IP  - 22
4099  - http://cancerres.aacrjournals.org/content/59/22/5830.short
4100  - http://cancerres.aacrjournals.org/content/59/22/5830.full
SO  - Cancer Res1999 Nov 15; 59
AB  - 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.