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.