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

Neovascularization and increased glycolysis, two universal characteristics of solid tumors, represent adaptations to a hypoxic microenvironment that a re correlated with tumor invasion, metastasis, and lethality, Hypoxia-induc ible factor 1 (HIF-1) activates transcription of genes encoding glucose tra nsporters, glycolytic enzymes, and vascular endothelial growth factor, HIF- 1 transcriptional activity is determined by regulated expression of the HIF -1 alpha subunit. In this study, HIF-1 alpha expression was analyzed by imm unohistochemistry in 179 tumor specimens. HIF-1 alpha was overexpressed in 13 of 19 tumor types compared with the respective normal tissues, including colon, breast, gastric, lung, skin, ovarian, pancreatic, prostate, and ren al carcinomas. HIF-1 alpha expression was correlated with aberrant p53 accu mulation and cell proliferation. Preneoplastic lesions in breast, colon, an d prostate overexpressed HIF-1 alpha, whereas benign tumors in breast and u terus did not. HIF-1 alpha overexpression was detected in only 29% of prima ry breast cancers but in 69% of breast cancer metastases. In brain tumors, HIF-1 alpha immunohistochemistry demarcated areas of angiogenesis, These re sults provide the first clinical data indicating that HIF-1 alpha may play an important role in human cancer progression.