Differential regulation of DEC2 among hypoxia-inducible genes in endometrial carcinomas.
Differential regulation of DEC2 among hypoxia-inducible genes in endometrial carcinomas.
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DOI：
10.3892/or.17.4.871
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发表时间：
2007-04
期刊：
影响因子：
4.2
通讯作者：
M. Yunokawa;K. Tanimoto;Hideaki Nakamura;N. Nagai;Y. Kudo;T. Kawamoto;Y. Kato;E. Hiyama;K. Hiyama;M. Nishiyama
中科院分区：
文献类型：
--
作者：
M. Yunokawa;K. Tanimoto;Hideaki Nakamura;N. Nagai;Y. Kudo;T. Kawamoto;Y. Kato;E. Hiyama;K. Hiyama;M. Nishiyama
在本研究中，我们证实了缺氧诱导因子-1(HIF-1)通路的激活在子宫内膜癌的发生和肿瘤表型发展中的重要作用，并提出了HIF-1靶基因--分化胚胎软骨细胞2(DEC2)在子宫内膜癌发生中的独特作用。低氧可导致4种子宫内膜癌细胞株HIF-1α蛋白表达增加。除SNG-M细胞中的DEC2外，其5个靶基因DEC1、DEC2、碳酸氢酶-9(CA9)、血管内皮生长因子(VEGF)和溶质载体家族2，成员1(SLC2A1)在大多数细胞系中的表达也呈反应性增加。DEC2、CA9和SLC2A1在4例不典型增生组织和82例子宫内膜癌组织中的表达水平显著高于21例正常子宫内膜组织。临床病理分析显示，VEGF和SLC2A1的表达与肿瘤的淋巴管侵犯状态和淋巴结转移密切相关。CA9和VEGF在绝经后肿瘤中的表达水平明显高于绝经前患者。SLC2A1的表达也与FIGO分期有关，而DEC2的表达与FIGO分级呈负相关。HIF-1通路的激活可能与子宫内膜癌的发生有关，其成分DEC2可能具有不同的表达调控机制和独特的致癌作用。
In this study, we demonstrate an important role of activation of the hypoxia-inducible factor-1 (HIF-1) pathway in endometrial carcinogenesis and tumor phenotype development of endometrial carcinoma, and suggest a unique role of the HIF-1-target gene, differentiated embryo chondrocyte 2 (DEC2), in carcinogenesis. Hypoxia caused an increase in HIF-1alpha protein expression in 4 endometrial carcinoma cell lines. The expressions of its 5 target genes - DEC1, DEC2, carbonic anhydrase-9 (CA9), vascular endothelial growth factor (VEGF), and solute carrier family 2, member 1 (SLC2A1) - also reactively increased in most of the cell lines, except for DEC2 in the SNG-M cells. The expression levels of DEC2, CA9, and SLC2A1 were significantly higher in the 4 atypical hyperplasia tissues and 82 endometrial carcinomas compared with those in the 21 normal endometria. Clinicopathological analyses of carcinoma patients revealed a significant correlation of the VEGF and SLC2A1 expression with the status of lymph-vascular involvement and lymph node metastasis. The expression levels of CA9 and VEGF were significantly higher in the tumors of post- as opposed to pre-menopausal patients. The SLC2A1 expression was also related to the FIGO stage, but the DEC2 expression was inversely related to the FIGO grade. The activation of the HIF-1 pathway could be related to endometrial carcinogenesis, and the component, DEC2, could have different expression-regulatory mechanisms and unique roles in carcinogenesis.