Department of Surgical Oncology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
J Gastroenterol. 2010 Sep;45(9):918-27. doi: 10.1007/s00535-010-0228-2. Epub 2010 Mar 25.
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.
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.
As compared to findings in the normal counterparts, AdipoR1 mRNA expression, standardized by β-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)-β in a dose-dependent manner.
Two major adiponectin receptors were decreased in gastric cancer as compared to findings in normal gastric epithelium. TGF-β 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.
脂联素已被证明对肿瘤的发展具有抑制作用，但肿瘤组织中脂联素受体的表达尚未完全阐明。本研究的目的是定量评估两种脂联素受体（AdipoR1 和 AdipoR2）在胃癌组织中的表达。
采用实时定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学染色方法，检测 67 例胃癌组织及其相应正常组织中 AdipoR1 和 AdipoR2 的 mRNA 水平。此外，还检测了细胞因子对培养的胃癌细胞中 AdipoR1 和 AdipoR2 表达的影响。
与相应的正常组织相比，AdipoR1 mRNA 表达（以 β-肌动蛋白 mRNA 标准化）呈下降趋势（癌组织 0.488±0.039，正常组织 0.955±0.281，p=0.0726），AdipoR2 表达明显降低（0.818±0.081，1.500±0.222，p=0.0035）。上皮细胞中 AdipoR1 和 AdipoR2 的免疫组织化学检测也显示出相同的趋势。此外，AdipoR2 在间质细胞中强烈表达。然而，这些受体的表达水平与各种病理因素之间没有很强的相关性。体外实验采用两种胃癌细胞系 MKN-74 和 NUGC-3，结果显示转化生长因子（TGF）-β呈剂量依赖性下调 AdipoR1 和 AdipoR2 的表达水平。
与正常胃上皮组织相比，胃癌中两种主要的脂联素受体表达降低。TGF-β可能参与了这种受体下调。这种下调可能是肿瘤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。
