The Expression and Distribution of the Hypoxia-Inducible Factors HIF-1alpha and HIF-2alpha in Normal Human Tissues, Cancers, and Tumor-Associated Macrophages Export

@article{citeulike:6071026, abstract = {The cellular response to hypoxia includes the hypoxia-inducible factor-1 (HIF-1)-induced transcription of genes involved in diverse processes such as glycolysis and angiogenesis. Induction of the HIF-regulated genes, as a consequence of the microenvironment or genetic changes, is known to have an important role in the growth of experimental tumors. Hypoxia-inducible factors 1{alpha} and 2{alpha} (HIF-1{alpha} and HIF-2{alpha}) are known to dimerize with the aryl hydrocarbon receptor nuclear translocator in mediating this response. Because regulation of the {alpha} chain protein level is a primary determinant of HIF activity, our aim was to investigate the distribution of HIF-1{alpha} and HIF-2{alpha} by immunohistochemistry in normal and pathological tissues using monoclonal antibodies (mAb). We raised a new mAb to detect HIF-1{alpha}, designated 122, and used our previously validated mAb 190b to HIF-2{alpha}. In the majority of solid tumors examined, including bladder, brain, breast, colon, ovarian, pancreatic, prostate, and renal carcinomas, nuclear expression of HIF-1{alpha} and -2{alpha} was observed in varying subsets of the tumor cells. HIF-2{alpha} 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-2{alpha} was strongly expressed.}, author = {Talks, Katherine L. and Turley, Helen and Gatter, Kevin C. and Maxwell, Patrick H. and Pugh, Christopher W. and Ratcliffe, Peter J. and Harris, Adrian L.}, citeulike-article-id = {6071026}, citeulike-linkout-0 = {http://ajp.amjpathol.org/content/157/2/411.abstract}, citeulike-linkout-1 = {http://ajp.amjpathol.org/content/157/2/411.full.pdf}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/10934146}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=10934146}, day = {1}, journal = {Am J Pathol}, keywords = {and, cancers, distribution, expression, factors, hif-1alpha, hif-2alpha, human, hypoxia-inducible, in, macrophages, normal, of, the, tissues, tumor-associated}, month = {August}, number = {2}, pages = {411--421}, posted-at = {2009-11-04 19:01:20}, priority = {2}, title = {The Expression and Distribution of the Hypoxia-Inducible Factors HIF-1{alpha} and HIF-2{alpha} in Normal Human Tissues, Cancers, and Tumor-Associated Macrophages}, url = {http://ajp.amjpathol.org/content/157/2/411.abstract}, volume = {157}, year = {2000} }

TY - JOUR ID - citeulike:6071026 L3 - citeulike-article-id:6071026 N2 - The cellular response to hypoxia includes the hypoxia-inducible factor-1 (HIF-1)-induced transcription of genes involved in diverse processes such as glycolysis and angiogenesis. Induction of the HIF-regulated genes, as a consequence of the microenvironment or genetic changes, is known to have an important role in the growth of experimental tumors. Hypoxia-inducible factors 1{alpha} and 2{alpha} (HIF-1{alpha} and HIF-2{alpha}) are known to dimerize with the aryl hydrocarbon receptor nuclear translocator in mediating this response. Because regulation of the {alpha} chain protein level is a primary determinant of HIF activity, our aim was to investigate the distribution of HIF-1{alpha} and HIF-2{alpha} by immunohistochemistry in normal and pathological tissues using monoclonal antibodies (mAb). We raised a new mAb to detect HIF-1{alpha}, designated 122, and used our previously validated mAb 190b to HIF-2{alpha}. In the majority of solid tumors examined, including bladder, brain, breast, colon, ovarian, pancreatic, prostate, and renal carcinomas, nuclear expression of HIF-1{alpha} and -2{alpha} was observed in varying subsets of the tumor cells. HIF-2{alpha} 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-2{alpha} was strongly expressed. IS - 2 JF - Am J Pathol EP - 421 TI - The Expression and Distribution of the Hypoxia-Inducible Factors HIF-1{alpha} and HIF-2{alpha} in Normal Human Tissues, Cancers, and Tumor-Associated Macrophages VL - 157 SP - 411 KW - and KW - cancers KW - distribution KW - expression KW - factors KW - hif-1alpha KW - hif-2alpha KW - human KW - hypoxia-inducible KW - in KW - macrophages KW - normal KW - of KW - the KW - tissues KW - tumor-associated AU - Talks, Katherine AU - Turley, Helen AU - Gatter, Kevin AU - Maxwell, Patrick AU - Pugh, Christopher AU - Ratcliffe, Peter AU - Harris, Adrian PY - 2000/08/01/ UR - http://ajp.amjpathol.org/content/157/2/411.abstract ER -