The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages
The expression and distribution of the hypoxia-inducible factors HIF-1α and HIF-2α in normal human tissues, cancers, and tumor-associated macrophages
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DOI：
10.1016/s0002-9440(10)64554-3
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发表时间：
2000-08-01
影响因子：
6
通讯作者：
Harris, AL
中科院分区：
文献类型：
--
作者：
Talks, KL;Turley, H;Harris, AL
细胞对缺氧的反应包括缺氧诱导因子-1（HIF-1）诱导的参与糖酵解和血管生成等多种过程的基因转录。作为微环境或遗传变化的结果，HIF调节基因的诱导已知在实验性肿瘤的生长中具有重要作用。已知缺氧诱导因子1 α和2 α（HIF-1 α和HIF-2 α）在介导该反应中与芳烃受体核转位蛋白二聚化。由于α链蛋白水平的调节是HIF活性的主要决定因素，我们的目的是通过使用单克隆抗体（mAb）的免疫组织化学方法来研究HIF-1 α和HIF-2 α在正常和病理组织中的分布。我们提出了一种新的用于检测HIF-1 α的mAb，命名为122，并使用我们先前验证的用于检测HIF-2 α的mAb 190 b。在检查的大多数实体瘤中，包括膀胱癌、脑癌、乳腺癌、结肠癌、卵巢癌、胰腺癌、前列腺癌和肾癌，在不同的肿瘤细胞亚群中观察到HIF-1 α和HIF-2 α的核表达。肿瘤相关巨噬细胞亚群也强烈表达HIF-2 α，有时在没有任何肿瘤细胞表达的情况下。在肿瘤内的其他基质细胞和邻近肿瘤边缘的正常组织中观察到较少的染色。相比之下，在正常组织中，除了在骨髓巨噬细胞亚群中，HIF-2 α强烈表达外，两种分子都检测不到。
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.