Expression of two isozymes of acyl-coenzyme A: Cholesterol acyltransferase-1 and -2 in clear cell type renal cell carcinoma
Expression of two isozymes of acyl-coenzyme A: Cholesterol acyltransferase-1 and -2 in clear cell type renal cell carcinoma
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DOI：
10.1111/j.1442-2042.2007.01947.x
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发表时间：
2008-02-01
影响因子：
2.6
通讯作者：
Ueda, Shoichi
中科院分区：
文献类型：
--
作者：
Matsumoto, Kenshi;Fujiwara, Yukio;Ueda, Shoichi
目的：研究透明细胞型肾细胞癌（RCC）中酰基辅酶A：胆固醇酰基转移酶-1 （ACAT-1）和-2的表达。方法：选取19例手术患者（28 ~ 85岁）的透明细胞型肾细胞癌及相应的正常肾组织标本。用抗ACAT-1和抗ACAT-2抗体免疫印迹法检测组织提取物的ACAT活性和蛋白表达。冷冻切片进行油红O染色检测脂质，并用acat特异性抗体进行免疫染色。结果：透明细胞癌中酰基辅酶A胆固醇酰基转移酶活性（23.52 +/- 4.90 pmol/mg protein/min）比正常肾（4.12 +/- 0.36）高5.7倍（P < 0.01）。与此一致的是，免疫印迹和免疫组织化学染色显示，ACAT-1在透明细胞型RCC中表达强烈。密度分析显示，ACAT-1在透明细胞型肾癌中的表达比正常肾高2.9倍。相比之下，ACAT-2在透明细胞型肾癌和正常肾脏中表达为阴性。油红O染色显示细胞内有大量脂质沉积。结论：我们在透明细胞型RCC中发现了ACAT-1的强表达。ACAT-1的上调导致ACAT酶活性升高，从而加速透明细胞型RCC中胆固醇酯的积累。
Objectives: The present study investigated the expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) and -2 in clear cell type renal cell carcinoma (RCC).Methods: Clear cell type RCC and corresponding normal kidney tissue samples were obtained from 19 surgical cases (28-85 years of age). Tissue extracts were assayed for ACAT activity and protein expression by immunoblotting with anti-ACAT-1 and anti-ACAT-2 antibodies. Frozen sections were subjected to Oil red O staining for lipids, and were immunostained with ACAT-specific antibodies.Results: Acyl-coenzyme A cholesterol acyltransferase activity was 5.7-fold higher (P < 0.01) in clear cell carcinoma (23.52 +/- 4.90 pmol/mg protein/min) than in normal kidney (4.12 +/- 0.36). Consistent with this, immunoblotting and immunohistochemical staining revealed strong expression of ACAT-1 in clear cell type RCC. Densitometric analysis showed that ACAT-1 expression was 2.9-fold higher in clear cell type RCC than in normal kidney. In contrast, ACAT-2 expression was negative in clear cell type RCC and normal kidney. Oil red O staining showed massive deposits of lipid in RCC cells.Conclusions: We identified strong expression of ACAT-1 in clear cell type RCC. Upregulation of ACAT-1 leads to high ACAT enzymatic activity, which accelerates the accumulation of cholesterol ester in clear cell type RCC.