Adiponectin receptors are downregulated in human gastric cancer
Adiponectin receptors are downregulated in human gastric cancer
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DOI：
10.1007/s00535-010-0228-2
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发表时间：
2010-09-01
影响因子：
6.3
通讯作者：
Nagawa, Hirokazu
中科院分区：
文献类型：
--
作者：
Otani, Kensuke;Kitayama, Joji;Nagawa, Hirokazu
背景脂联素对肿瘤的发生、发展具有抑制作用，但脂联素受体在肿瘤组织中的表达尚未完全阐明。本研究旨在定量检测AdipoR1和AdipoR2两种脂联素受体在胃癌组织中的表达。方法采用定量逆转录聚合酶链式反应(RT-PCR)和免疫组织化学方法检测67例胃癌组织和正常组织中AdipoR1和AdipoR2的mRNA水平。结果与正常胃癌细胞相比，经β-肌动蛋白信使其标准化后，胃癌组织中AdipoR1mRNA表达降低(癌组织为0.488+/-0.039，正常组织为0.955+/-0.281，p=0.0726)，而AdipoR2表达明显降低(0.818+/-0.081，1.500+/-0.222，p=0.0035)。免疫组织化学检测显示AdipoR1和AdipoR2在上皮细胞中的表达趋势相同。此外，AdipoR2在间质细胞中呈强阳性表达。然而，这些受体的表达水平与各种病理因素的相关性不强。体外培养的MKN-74和NUGC-3细胞的实验表明，转化生长因子-β显著降低AdipoR1和AdipoR2的表达水平，且呈剂量依赖关系。结论与正常胃上皮细胞相比，胃癌组织中两种主要的脂联素受体表达水平降低。转化生长因子-β可能参与了这种受体的下调。这种下调可能是癌细胞在肿瘤发展的初始阶段逃避脂联素抗增殖作用的理想策略。
Background Adiponectin has been shown to have suppressive effects on tumor development, but the expression of adiponectin receptors in tumor tissue has not been fully elucidated. The purpose of this study was to quantitatively evaluate the expression of two adiponectin receptors, AdipoR1 and AdipoR2, in gastric cancer tissue.Methods The mRNA levels of AdipoR1 and AdipoR2 were evaluated by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining in 67 gastric cancer tissues and their normal counterparts. In addition, the effects of cytokines on AdipoR1 and AdipoR2 expression in cultured gastric cancer cells were examined.Results As compared to findings in the normal counterparts, AdipoR1 mRNA expression, standardized by beta-actin mRNA, tended to be lower (cancer 0.488 +/- 0.039, normal 0.955 +/- 0.281, p = 0.0726) and AdipoR2 expression was significantly lower (0.818 +/- 0.081, 1.500 +/- 0.222, p = 0.0035) in gastric cancer tissue. Immunohistochemical examination showed the same tendency for AdipoR1 and AdipoR2 expression in epithelial cells. Moreover, AdipoR2 was strongly expressed in interstitial cells. However, the expression levels of these receptors did not show a strong correlation with various pathological factors. An in vitro experiment using two gastric cancer cell lines, MKN-74 and NUGC-3, showed that the expression levels of AdipoR1 and AdipoR2 were significantly decreased by transforming growth factor (TGF)-beta in a dose-dependent manner.Conclusions Two major adiponectin receptors were decreased in gastric cancer as compared to findings in normal gastric epithelium. TGF-beta may be involved in this receptor downregulation. This downregulation may be an ideal strategy for cancer cells to escape the antiproliferative effects of adiponectin in the initial phase of tumor development.