HIF-2alpha (hypoxia-inducible factor-2 alpha) Antibody Review





  • Hypoxia-inducible factors (HIF-1alpha and HIF-2alpha) are closely related protein complexes that activate transcription of target genes in response to hypoxia. PMID: 17033215

Abnormal Expression

  • In tumor cells, low HIF-2alpha expression was observed in 6.3%, moderate in 31.9% and high in 61.8% of the cases. A trend of correlation of this expression with MVD was observed. In addition, HIF-2alpha expression was positively correlated with thymidine phosphorylase and fibronectin expression. A lower HIF-2alpha expression was detected in tumors that recurred earlier in univariate methods of analysis. HIF-2alpha was expressed in tumor stroma associated cells in 53.5% of specimens and was correlated with advance tumor stage, thymidine phosphorylase and tenascin expression. PMID: 17033215

  • HIF-2alpha is specifically expressed and appears to be involved in the development of the murine sympathetic nervous system (SNS). HIF-2alpha was detected in hypoxic and in well-oxygenized neuroblastoma cells and tissue, presumably reflecting their embryonic features. PMID: 15652356

  • HIF-2alpha/EPAS1 is expressed in most of hepatocellular carcinoma (HCC) with capsular infiltration and portal vein invasion, which indicates a possible role of HIF-2alpha/EPAS1 in HCC metastasis. PMID: 14966910

  • Although HIF-2alpha was not detectable under baseline conditions, marked hypoxic induction occurred in all organs investigated, including brain, heart, lung, kidney, liver, pancreas, and intestine. Immunohistochemistry revealed nuclear accumulation in distinct cell populations of each tissue, which were exclusively non-parenchymal in some organs (kidney, pancreas, and brain), predominantly parenchymal in others (liver and intestine) or equally distributed (myocardium). PMID: 12490539

  • HIF-2alpha/EPAS1 is mostly expressed in invasive bladder cancer, which indicates a possible role for HIF-2alpha/EPAS1 in the invasion of bladder cancer. PMID: 11992927

  • Overexpression of HIF-1alpha and HIF-2alpha was demonstrated in three head and neck squamous cell carcinoma (HNSCC) cell lines under hypoxia and tumor tissue versus normal tissue (n = 20, HIF-1alpha, P = 0.023; HIF-2alpha, P = 0.013). On immunostaining, HIF-1alpha and HIF-2alpha expression were localized to tumor nuclei; HIF-2alpha expression was also seen in tumor-associated macrophages. PMID: 11980639

  • Considering all 48 paired placental biopsy sites (eight sites each for six normal term and six preeclamptic placentas), HIF-2alpha protein levels in the preeclamptic placentas exceeded those in the normal term placentas in 39, or 81%, of the paired sites (P: < 0.0013). The HIF-2alpha immunoreactivity was mainly located in the nuclei of the syncytiotrophoblast and fetoplacental vascular endothelium in the preeclamptic villous placenta. We conclude that protein expression of HIF-2alpha, but not of HIF-1alpha or -1beta, is selectively increased in the preeclamptic placenta. The molecular mechanism(s) of this abnormality as well as the genes affected downstream are currently under investigation. To our knowledge, this is the first report of abnormal HIF-2alpha expression in human disease other than cancer. PMID: 11159352

  • In the majority of solid tumors examined, including bladder, brain, breast, colon, ovarian, pancreatic, prostate, and renal carcinomas, nuclear expression of HIF-1alpha and -2alpha was observed in varying subsets of the tumor cells. HIF-2alpha was also strongly expressed by subsets of tumor-associated macrophages, sometimes in the absence of any tumor cell expression. Less frequently staining was observed in other stromal cells within the tumors and in normal tissue adjacent to tumor margins. In contrast, in normal tissue neither molecule was detectable except within subsets of bone marrow macrophages, where HIF-2alpha was strongly expressed. PMID: 10934146


  • additive effect of HIF-2alpha on poor prognosis suggested that different pathways may be regulated by HIF-2alph. PMID: 16826581

  • HIF-2alpha is not transcriptionally active in embryonic stem (ES) cells, as well as possible inhibition by a HIF-2alpha-specific transcriptional repressor. PMID: 16611993

  • HIF-2alpha can regulate stem cell function and/or differentiation through activation of Oct-4, which in turn contributes to HIF-2alpha's tumor promoting activity. PMID: 16510872

  • These data demonstrate an intrinsic requirement for Hif-2alpha by endothelial cells and imply that hypoxia may control endothelial functions directly via Hif-2alpha-regulated Tie-2 expression. PMID: 15851592

  • HIF-2alpha may be more important in the survival response to environmental variables other than the level of oxygen. PMID: 11546756



Immunohistochemistry (IHC)

  • Expression of HIF-2alpha/EPAS1 was investigated immunohistochemically on paraffin-embedded sections from 97 patients with hepatocellular carcinoma (HCC). PMID: 14966910

  • Expression of HIF-2alpha/EPAS1 protein was also investigated immunohistochemically on paraffin-embedded sections from 24 patients with bladder cancer. PMID: 11992927

  • our aim was to investigate the distribution of HIF-1alpha and HIF-2alpha by immunohistochemistry in normal and pathological tissues using monoclonal antibodies (mAb). PMID: 10934146

Western Blot (WB)

  • Two bladder cancer cell lines (T24, EJ-1) were examined for the expression of HIF-2alpha/EPAS1 mRNA by reverse transcriptase-polymerase chain reaction and HIF-2alpha/EPAS1 protein by Western blot analysis, respectively. PMID: 11992927