Up-regulation of hypoxia-inducible factor 1α is an early event in prostate carcinogenesis
Up-regulation of hypoxia-inducible factor 1α is an early event in prostate carcinogenesis
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DOI：
10.1016/j.cdp.2003.12.009
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发表时间：
2004-01-01
影响因子：
--
通讯作者：
De Marzo, AM
中科院分区：
文献类型：
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作者：
Zhong, H;Semenza, GL;De Marzo, AM
d缺氧诱导因子 1 (HIF-1) 激活编码葡萄糖转运蛋白、糖酵解酶和血管内皮生长因子 (VEGF) 的基因的转录。 HIF-1α 是 HIF-1 异二聚体的主要亚基。在这项研究中，HIF-1α的免疫组织化学分析集中于含有高级别前列腺上皮内瘤变病变的临床标本，因为高级别前列腺上皮内瘤变被认为是大多数侵袭性前列腺腺癌的前兆，并且呈现血管生成活性增加。在总共 10 个前列腺活检中发现的 14 个高级前列腺上皮内瘤变病变中，有 11 个病变相对于正常上皮、基质细胞和良性前列腺增生 (BPH) 均上调。此外，在高级别上皮内瘤变中，邻近前列腺癌病变中 HIF-1α 的上调更为增强。结果表明，HIF-1α的上调是前列腺癌发生的早期事件，并且HIF-1α可能成为预防前列腺癌的潜在靶点和监测前列腺癌前病变的替代生物标志物。 (C) 2004 年由 Elsevier Ltd. 代表国际预防肿瘤学会出版。
dHypoxia-inducible factor 1 (HIF-1) activates the transcription of genes encoding glucose transporters, glycolytic enzymes, and vascular endothelial growth factor (VEGF). HIF-1alpha is a major subunit of HIF-1 heterodimer. In this study, an immunohistochemical analysis of HIF-1alpha was focused on clinical specimens containing high-grade prostate intraepithelial neoplasia lesions since high-grade prostate intraepithelial neoplasia is considered the precursor of a majority of invasive prostate adenocarcinoma and presents the increased activity of angiogenesis. HIF-1alpha was up-regulated in 11 of 14 high-grade prostate intraepithelial neoplasia lesions identified in a total 10 prostate biopsies relative to the respective normal epithelium, stromal cells, and benign prostatic hyperplasia (BPH). Moreover, up-regulation of HIF-1alpha in adjacent prosate cancer lesions was more enhanced in high-grade intraepithelial neoplasia. The results suggest that up-regulation of HIF-1alpha is an earlyevent in prostatecarcinogenesis, and that HIF-1alpha may become a potential target for prostate cancer prevention and a surrogate biomarker for monitoring pre-malignant lesions of the prostate. (C) 2004 Published by Elsevier Ltd. on behalf of Inernational Society for Preventive Oncology.