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人食管鳞状细胞癌中花生四烯酸代谢相关基因的失调

The deregulation of arachidonic acid metabolism-related genes in human esophageal squamous cell carcinoma.

作者信息

Zhi Huiying, Zhang Jian, Hu Gengxi, Lu Jiayun, Wang Xiuqin, Zhou Chuannong, Wu Min, Liu Zhihua

机构信息

National Lab of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100 021, People's Republic of China.

出版信息

Int J Cancer. 2003 Sep 1;106(3):327-33. doi: 10.1002/ijc.11225.

Abstract

Esophageal squamous cell carcinoma (ESCC) is 1 of the most common cancers worldwide. In our study, cDNA microarray comprising 14,803 genes was employed to identify gene-specific expression profile in 6 paired samples of ESCC. Nine genes identified were commonly upregulated and 36 downregulated in tumors, as compared to normal esophageal squamous epithelia. Among these genes, we found that 9 of the altered expression genes were related to arachidonic acid (AA) metabolism, such as annexin-I, annexin-II, S100A8, S100A10, S100P, glutathione peroxidase-3, phosphatidylcholine transfer protein, aldo-keto reductase family 1 and cyclooxygenase-2 (COX-2). To gain insights into the regulation of the AA metabolism pathway involved in the carcinogenesis of ESCC, we investigated the expression of 8 genes related to the AA metabolism by semiquantitative reverse transcript (RT)-PCR and/or Western blot and immunohistochemistry. These genes include annexin-I, annexin-II, COX-2, cyclooxygenase-1 (COX-1) and cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP) and 12-lipoxygenase (12-LOX) (not included in the array data). The expression level of annexin-I, annexin-II was downregulated in esophageal cancer, whereas cPLA(2), FLAP, COX-2, 5-LOX and 12-LOX were upregulated. These data suggested that AA metabolism pathway and its altered expression may contribute to esophageal squamous cell carcinogenesis.

摘要

食管鳞状细胞癌(ESCC)是全球最常见的癌症之一。在我们的研究中,使用包含14,803个基因的cDNA微阵列来鉴定6对ESCC样本中的基因特异性表达谱。与正常食管鳞状上皮相比,在肿瘤中鉴定出的9个基因通常上调,36个基因下调。在这些基因中,我们发现9个表达改变的基因与花生四烯酸(AA)代谢相关,如膜联蛋白-I、膜联蛋白-II、S100A8、S100A10、S100P、谷胱甘肽过氧化物酶-3、磷脂酰胆碱转移蛋白、醛糖酮还原酶家族1和环氧化酶-2(COX-2)。为了深入了解参与ESCC致癌过程的AA代谢途径的调控,我们通过半定量逆转录(RT)-PCR和/或蛋白质印迹及免疫组织化学研究了8个与AA代谢相关基因的表达。这些基因包括膜联蛋白-I、膜联蛋白-II、COX-2、环氧化酶-1(COX-1)和胞质磷脂酶A2(cPLA2)、5-脂氧合酶(5-LOX)、5-脂氧合酶激活蛋白(FLAP)和12-脂氧合酶(12-LOX)(未包含在阵列数据中)。食管癌中膜联蛋白-I、膜联蛋白-II的表达水平下调,而cPLA2、FLAP、COX-2、5-LOX和12-LOX上调。这些数据表明AA代谢途径及其表达改变可能有助于食管鳞状细胞癌的发生。

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