Expression of two isozymes of acyl-coenzyme A: Cholesterol acyltransferase-1 and -2 in clear cell type renal cell carcinoma |
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Authors: | Kenshi Matsumoto Yukio Fujiwara Ryoji Nagai Masaki Yoshida Shoichi Ueda |
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Institution: | Departments of Urology and;Medical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Honjo, Kumamoto, Japan |
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Abstract: | 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. |
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Keywords: | acyl-coenzyme A: cholesterol acyltransferase cholesterol accumulation clear cell type lipid droplet renal cell carcinoma |
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