RT Journal Article
SR Electronic
T1 Overexpression of Hypoxia-inducible Factor 1α in Common Human Cancers and Their Metastases
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 5830
OP 5835
VO 59
IS 22
A1 Zhong, Hua
A1 De Marzo, Angelo M.
A1 Laughner, Erik
A1 Lim, Michael
A1 Hilton, David A.
A1 Zagzag, David
A1 Buechler, Peter
A1 Isaacs, William B.
A1 Semenza, Gregg L.
A1 Simons, Jonathan W.
YR 1999
UL http://cancerres.aacrjournals.org/content/59/22/5830.abstract
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.