HIF-1alpha (hypoxia-inducible factor-1 alpha) Antibody Review





  • The hypoxia-inducible factors (HIF) are alpha/beta heterodimeric transcription factors of the basic helix-loop-helix-Per-Arnt-Sim (bHLH-PAS) superfamily and are chiefly responsible for cellular adaptation to oxygen deprivation. HIF function relies on the stabilization of the alpha subunit. When oxygen tension falls, HIF-alpha subunits translocate to the nucleus and, upon dimerization with HIF-beta, activate transcription of target genes, including vascular endothelial growth factor, vascular endothelial growth factor receptor-1 and -2, and WT-1, which are vital for kidney development. HIF-beta subunits are stable regardless of oxygen concentration and constitutively translocate to the nucleus. It was shown previously that HIF-1beta protein expression is nearly ubiquitous in newborn kidney and that HIF-1beta dimerizes with either HIF-1alpha or -2alpha. PMID: 15466261

  • an endogenous hypoxia marker and associated radioresistance.. PMID: 15935515, PMID: 12829158

  • the oxygen-regulated subunit of HIF-1, which regulates the transcription of genes involved in oxygen homeostasis in response to hypoxia. PMID: 17045424

  • a key element in allowing cells to adapt and survive in a hostile hypoxic environment via a variety of pathways. PMID: 16889900

  • plays a key role in responses to hypoxia and expression of HIF-1alpha downstream genes leads to both an adapted metabolism and increased oxygen supply. PMID: 16847924

  • a protein of cellular response to hypoxia. PMID: 16886625

  • a central component of the oxygen sensing system that coordinates cellular responses to conditions of decreased oxygen availability. PMID: 16842205

  • regulates vascular endothelial growth factor (VEGF), the presumed principal mediator of angiogenesis in malignant gliomas, under normal physiologic conditions. PMID: 16612574, PMID: 16515634, PMID: 15475194, PMID: 11691837

  • an oxygen-dependent transcriptional activator, plays a major role in tumor angiogenesis and in the response of tumors to hypoxia, and it is mainly responsible for the "angiogenic switch". PMID: 16294030, PMID: 16280300

  • a potential endogenous marker of tumor hypoxia and therapeutic target. PMID: 16253768, PMID: 15313932

  • a transcription factor that is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. PMID: 15849727

  • a transcription factor that plays a regulatory role in the expression of VEGF. PMID: 14675669

  • HIF-1 complex is composed of two b-HLH proteins: HIF-1beta that is constitutively expressed, and HIF-1alpha, that is present only in hypoxic cells. PMID: 9660756, PMID: 16889900

Normal Expression

  • HIF-1alpha immunoreaction was recognized through nuclear staining of positive cells. PMID: 16886625

  • Normally, HIF-1alpha protein, the dominant subunit of HIF-1, is accumulated in nuclei when cells are exposed to hypoxia (1% O2) and rapidly degraded when cells are re-oxygenated. Here, we found that constitutive nuclear expression of HIF-1alpha protein was a general phenomenon in vitro under normoxic conditions in human malignant cells including those derived from the hematopoietic system, such as lymphoma and leukemia cells. PMID: 12175540

  • HIF-1alpha expression was liver and blood specific. PMID: 17045424

  • in normal tissue neither HIF-1alpha nor HIF-2alpha molecule was detectable except within subsets of bone marrow macrophages, where HIF-2alpha was strongly expressed. PMID: 10934146

  • expression pattern of HIF1alpha in both epithelial and mesenchymal structures of the chicken embryo through the first 7 days of development is reported here. HIF1alpha transcript is expressed diffusely throughout the neuroepithelium, limb, mesonephritic and cephalic mesenchyme, progressively becoming restricted to known proliferative zones of the central nervous system. Specific, strong expression is unexpectedly found in the endoderm of Sessel's pouch and in the ectoderm of both Rathke's pouch and the first branchial arch before the disappearance of the buccopharyngeal membrane. PMID: 12609602

  • aHIF is widely expressed in normal foetal and adult human tissues as in tumour tissues. Foetal aHIF expression level is higher than adult one and high enough to affect the HIF-1alpha mRNA/aHIF transcripts ratio. PMID: 12459261

Abnormal Expresion

  • Nuclear HIF-1alpha expression in tumor cells was detected in 57.1% of 144 bladder cancer cases. A trend of correlation of this expression with poorly differentiated tumors was observed. PMID: 17033215

  • HIF-1alpha expression in colorectal carcinoma was significantly higher than in non-neoplasm colorectal mucosa. PMID: 16937436

  • HIF-1alpha was detected only in astrocytic gliomas grades III and IV, both in the nucleus and in the cytoplasm. PMID: 16724682

  • Overexpression of HIF-1alpha in gastric carcinomas may upregulate its downstream gene products leading to VEGF-mediated angiogenesis, and resulting in a poor prognosis for patients. PMID: 16847924

  • HIF-1alpha staining was found mainly in the cytoplasm. The tumours were subdivided into HIF-1alpha(LOW) and HIF-1alpha(HIGH) on the basis of staining intensity. PMID: 16814458

  • It is concluded that in normal cardiac fibers, basal expression of HIF-1alpha is not appreciable, but it steadily increases after ischemia. PMID: 16423235

  • HIF-1alpha is commonly expressed in Malignant pleural mesothelioma (MPM) but not in normal mesothelium, consistent with the presence of hypoxia. PMID: 16169121

  • we report that in old rat cerebral cortex exposed to hypoxia, the accumulation in the cytoplasm of hypoxic inducible factor 1alpha (HIF-1alpha)--the master regulator of oxygen homeostasis--concomitant with p66(Shc) activation and reduced IkBalpha phosphorylation is associated with tissue apoptosis or necrosis. PMID: 16026332

  • Under hypoxic conditions, HIF-1alpha is stabilized and enters the nucleus, to form a dimer with HIF-1beta, where it induces the expression of its target genes. PMID: 15368959

  • HIF-1alpha immunoreactivity, confined to the nucleoplasm, was present in both tumor and vascular endothelial cells. PMID: 16199897

  • Thirty-two of the 82 (39%) tumour specimens showed high levels of HIF-1alpha immunoreactivity in the nuclei and/or cytoplasm of cancer cells. PMID: 15288294

  • VEGF expression correlated with HIF-1alpha expression, suggesting that HIF-1alpha may contribute to the overexpression of VEGF observed in epithelial ovarian cancer. PMID: 14675669

  • immunoreactivity (IR) of HIF-1alpha was distributed numerously in the nuclei of glomus (type-I) and other cells since hypoxia for 1 day, but was faint and scattered in the normoxic CBs. PMID: 14609506

  • Focal adhesion kinase (FAK) and hypoxia-inducible factor (HIF-1alpha) are both up-regulated in glioblastoma multiforme (GBMs), particularly in invasive zones. PMID: 12811834

  • HIF-1alpha immunoreactivity was confined to the nucleoplasm whereas the nucleoli were unconspicuous. The distribution of HIF-1alpha was evident in the tumours whereas normal adenohypophysial cells showed no HIF-1alpha staining. HIF-1alpha expression was detected not only in the tumour cells but also in endothelial cells lining the blood vessels within the tumour. PMID: 12792878

  • 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. PMID: 10934146

  • normal prostates (NP) manifested no immunoreactivity, whereas prostate adenocarcinoma (Pca) and benign prostatic glandular hyperplasia (BPH) showed significantly increased HIF-1alpha protein expression. PMID: 14687488

  • HIF-1alpha was expressed abundantly by macrophages in most rheumatoid synovia, predominantly close to the intimal layer but also in the subintimal zone. There was markedly lower expression of HIF-1alpha in OA synovia, and it was absent from all of the healthy synovia. PMID: 11465705

  • transplanted islets strongly express HIF-1alpha in association with beta-cell death and decreased insulin production until adequate revascularization is established and (2) early suppression of HIF-1alpha results in less beta-cell death thereby minimizing early graft failure. PMID: 17049056

Expression Alteration

  • Aluminum toxicity creates hypoxic environment that promotes the translocation of HIF-1alpha to the nucleus and stimulates the anaerobic metabolism of D-glucose. PMID: 16979867

  • UV radiation induced HIF-1alpha and VEGF protein expression in a dose- and time-dependent manner in cultured human keratinocytes. PMID: 16964427

  • Our results showed that green tea extract and EGCG significantly inhibited hypoxia- and serum-induced HIF-1alpha protein accumulation in these cancer cells but had no effects on HIF-1alpha mRNA expression. PMID: 16731755

  • Hyperbaric oxygen reduced early APAP-induced hepatocellular injury. APAP poisoning increases HIF-1alpha protein levels and functional activity. HBO2 increases HIF-1alpha protein levels and DNA binding without a corresponding increase in transcriptional activity. PMID: 16636360

  • We demonstrate that noscapine treatment of human glioma U87MG and T98G cell lines exposed to the hypoxic mimetic agent, CoCl2, inhibits hypoxia-mediated HIF-1alpha expression and transcriptional activity as measured by decreased secretion of VEGF, a HIF-1 target gene. PMID: 16596228

  • HIF-1alpha concentrations increase during breast carcinogenesis, and are associated with poor prognosis. PMID: 15677538

  • both normal and malignant chondrocytes increased HIF-1alpha protein expression in an oxygen concentration dependent manner and also increased VEGF mRNA expression in response to hypoxia. PMID: 15475194

  • HIF-1alpha protein was detectable in wound cells 1 and 5 days after injury. PMID: 11698256

  • NO does not only modulate the HIF-1 response under hypoxic conditions, but it also functions as a HIF-1 inducer. We conclude that accumulation of HIF-1 occurs during hypoxia but also under inflammatory conditions that are characterized by sustained NO formation. PMID: 11159530

  • significant evaluation in HIF-1alpha expression was revealed in regenerating rat livers. HIF-1alpha expression was preceded by VEGF and flt-1 expression and thus may be related to sinusoidal endothelial reconstruction. PMID: 16162160


  • under hypoxia, hypoxia-inducible factor 1alpha has a significantly prolonged half-life and up-regulates a number of hypoxia genes. PMID: 17028170

  • HIF-1alpha polymorphisms may have an important impact on HIF-protein stability and, eventually, function. PMID: 16837101

  • HIF-1alpha are critical regulators of endochondral bone development. PMID: 16831906

  • HIF-1alpha alone was associated with a worse disease-specific survival (DSS) (P =.05) and disease-free survival (DFS) (P = .03) in multivariate analyses. PMID: 16826581

  • HIF-1alpha upgrades many gene products which include the glucose transporter protein 1 (Glut-1). PMID: 16142350

  • the use of HIF-1alpha as an indicator of tumor hypoxia and aggressiveness as well as development of hypoxia-directed antitumor therapies based on the expression of HIF-1alpha. PMID: 16103077

  • HIF-1alpha is associated with a worse prognosis in patients with invasive breast carcinoma. Furthermore HIF-1alpha immunodetection may be considered as a potential indicator for selecting patients who could benefit from specific therapies interfering with HIF-1alpha pathway. PMID: 15849727

  • HIF-1alpha can prompt apoptotic cell death after experimental traumatic brain injury. PMID: 11835736

  • HIF-1 may be the major hypoxia-inducible transcription factor in macrophages and that HIF-1-regulated constructs are likely to be effective in macrophage delivery of hypoxia-regulated gene therapy to human tumours. PMID: 11793372

  • HIF-1alpha is considered to be a useful independent prognostic factor in gastric cancer, and the combination of a HIF-1alpha protein overexpression with nonfunctional p53 tends to indicate a dismal prognosis. PMID: 16951228

  • HIF-1alpha as regulator of tumor-associated lymphangiogenesis in human breast cancer and emphasizes the promising status of HIF-1alpha as a therapeutical target against tumor progression and metastasis. PMID: 16555123, PMID: 16011605

  • HIF-1alpha may play a role in angiogenesis and tumor progression via regulation of VEGF in human colorectal carcinoma. PMID: 12673675




  • We developed and validated an enzyme-linked immunosorbent assay (ELISA) approach to measure HIF-1alpha levels in cultured tumor cell lines in vitro. PMID: 15879029

  • HIF-1alpha expression and VEGF secretion in glioma cell lines under normoxia and hypoxia were examined using ELISA and Western blot. PMID: 16612574

Flow Cytometry (FC)

  • HIF-1alpha expression following in vitro hypoxia was measured in U87 MG glioblastoma cells by Western blot and flow cytometry. PMID: 12829158

Gel Shift Assay (Gel)

  • Expression and function of HIF-1alpha were assessed by immunofluorescence microscopy, Western blot analysis, gel shift assays, and luciferase reporter assays. PMID: 16408279

Immunofluorescence (IF)

  • Expression and function of HIF-1alpha were assessed by immunofluorescence microscopy, Western blot analysis, gel shift assays, and luciferase reporter assays. PMID: 16408279

  • indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1alpha and 2alpha in clear cell renal carcinoma cells. PMID: 16600797

Immunocytochemistry (ICC)

  • regional localization of HIF-1alpha mRNA and protein was determined by in situ hybridization and immunocytochemistry in adult male rats exposed to moderate hypoxia (10% O2) for 1-6 h. HIF-1alpha protein was found in cell types identified by immunocytochemistry as catecholaminergic neurons. PMID: 11860493

Immunohistochemistry (IHC)

  • expression of HIF-1alpha was assessed by immunohistochemistry in 187 patients with T(2-4) N(0-1) breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. PMID: 16899602

  • HIF-1alpha expression using immunohistochemistry and related the results to RCC type and clinicopathologic variables. PMID: 16814458

  • Sixty-three human astrocytic gliomas were analyzed by immunohistochemistry for HIF-1alpha and iNOS using formalin-fixed paraffin-embedded material. PMID: 16724682

  • HIF-1alpha expression in human ischemic hearts with the ABC-inmunohistochemistry technique and amplification by biotinylated tyramide. PMID: 16423235

  • The immunohistochemical expression of HIF-1alpha and VEGF was evaluated in 30 formalin-fixed, paraffin-embedded postoperative rectal adenocarcinoma tissue samples. PMID: 16512994

  • Immunohistochemical studies using a monoclonal antibody specific for HIF-1alpha indicate that the overexpression of HIF-1alpha occurs in the most common forms of human cancer, including bladder cancer. PMID: 16142350

  • HIF-1alpha expression was investigated using immunohistochemical assays on frozen sections, and correlated with patients' outcome (median follow-up = 13.5 years). PMID: 15849727

  • HIF-1alpha protein expression was determined by immunohistochemistry in formalin-fixed and paraffin-embedded specimens obtained from 13 cases of NP, 28 cases of BPH, and 34 cases of Pca. PMID: 14687488

  • We investigated HIF-1alpha expression immunohistochemically in pancreatic carcinoma tissues and regional lymph node metastasis. PMID: 14636255

  • HIF-1alpha, CA IX, and GLUT-1 expression was studied by immunohistochemistry, including double staining for CA IX and HIF-1alpha. PMID: 15677538

  • Using immunohistochemistry, we have now analyzed the spatial distribution of HIF-1alpha and its target genes in normal cartilage and in cartilage from knee joints with osteoarthritis. PMID: 15611874

  • Accumulation of HIF1alpha and HIF2alpha was detected immunohistochemically in a series of 46 nodular malignant melanomas of the skin (epithelioid cell variant), treated with wide local excision. PMID: 14512791

  • expression of HIF-1alpha and apoptosis in 37 samples of tissues around cerebral bleeding loci and 9 samples of normal cerebral tissues was assessed by immunohistochemical straining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling methods. PMID: 15587402

Western Blot (WB)

  • Western blotting studies demonstrate a significant increase in the expression of PHD-2 ( approximately 1.8-2-fold increase, at 0.5, 16 and 24 h after reoxygenation; p < 0.01) and HIF-1alpha (approximately 1.7-fold increase immediately after hypoxia; p < 0.05) proteins following hypoxic preconditioning relative to normoxic control tissue. PMID: 16828226

  • Using a left inguinal surgical incision, a 1 cm section of ISV was resected from each patient in both groups as specimens for immunoblotting and immunohistochemical staining of HIF-1alpha. PMID: 16469614

  • Western blot was used to examine the expression of HIF-1alpha in prostate cancer cell line (PC-3M) induced by different oxygen tension. PMID: 15791851

  • Two physiological situations were studied using HIF-1alpha-specific Western blotting and semiquantitative RT-PCR. PMID: 16043777

  • Northern and Western blot analysis were used to assess VEGF and HIF-1alpha expression in the different culture conditions. PMID: 15010293

  • Western blot analyses indicated that HIF-1alpha rapidly accumulated during the onset of hypoxia and did not fall for 14 days but fell to normal by 21 days despite the continuous low arterial oxygen tension. PMID: 11053346