Cytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer

Abstract

Introduction: Hypoxia-inducible factor (HIF)-1α levels in invasive breast carcinoma have been shown to be an adverse prognostic indicator. Cellular HIF-1α activity is regulated by factor-inhibiting hypoxia-inducible factor 1 (FIH-1). In hypoxia, FIH-1 hydroxylation of Asn803 within the C-terminal transactivation domain does not occur and HIF-1α forms a fully active transcriptional complex. The present study investigates the role of FIH-1 in invasive breast carcinoma and its correlation with hypoxia. Methods: Microarrayed tissue cores from 295 invasive carcinomas were stained for FIH-1, for HIF-1α and for carbonic anhydrase 9. FIH-1 expression was correlated with standard clinicopathological ..