Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 002215, USA.
Horm Cancer. 2010 Jun;1(3):136-45. doi: 10.1007/s12672-010-0017-7.
Adiponectin has been proposed to be a mediator of obesity-associated malignancies and to have direct antineoplastic effects acting via adiponectin receptors AdipoR1 and AdipoR2. We describe herein the expression of AdipoR1 and AdipoR2 in several cancers not previously studied. We used immunohistochemistry to assess expression of adiponectin receptors in archival specimens of renal cell carcinoma (n = 64), hepatocellular carcinoma (n = 123), melanoma (n = 20), cholangiocarcinoma (n = 20), transitional cell carcinoma of the bladder (n = 24), ovarian epithelial carcinoma (n = 63), cervical squamous cell carcinoma (n = 49), and adrenocortical carcinoma (n = 48). To compare expression in malignant versus nonmalignant tissues, we also studied AdipoR1 and AdipoR2 expression in pairs of renal cell carcinoma and adjacent healthy kidney tissue specimens by immunohistochemistry. We also studied mRNA expression in 45 specimens of renal cell carcinoma by real-time polymerase chain reaction. Finally, we utilized Western blotting to confirm the presence of adiponectin receptors and subsequently studied cell signaling pathways of adiponectin in the renal cancer cell line 786-O. Cancers associated with obesity were significantly more likely to express AdipoR1 than cancers not associated with obesity. Of the specimens of renal cell carcinoma, which is strongly associated with obesity, 93.8% expressed AdipoR1 compared to 44.9% of the specimens of cervical cell carcinoma, which is not associated with obesity (p < 0.001). There was no difference in the expression of adiponectin receptors or their mRNA between malignant and benign kidney tissue specimens. Overall, there were no correlations between expression of adiponectin receptors or their mRNA and tumor prognostic factors. Finally, Western blotting confirmed the presence of AdipoR1 in the renal cancer cell line 786-O, and adiponectin activates in vitro several signaling pathways in this cell line. In summary, we report for the first time expression of AdipoR1 and AdipoR2 in the above cancers and that AdipoR1 is more ubiquitously expressed in obesity-associated cancers.
脂联素被认为是肥胖相关恶性肿瘤的介质，并通过脂联素受体 AdipoR1 和 AdipoR2 发挥直接的抗肿瘤作用。我们在此描述了几种以前未研究过的癌症中 AdipoR1 和 AdipoR2 的表达情况。我们使用免疫组织化学方法评估了 64 例肾细胞癌、123 例肝细胞癌、20 例黑色素瘤、20 例胆管癌、24 例膀胱癌、63 例卵巢上皮癌、49 例宫颈鳞状细胞癌和 48 例肾上腺皮质癌的脂肪细胞受体的表达。为了比较恶性组织和非恶性组织中的表达情况，我们还通过免疫组织化学方法研究了配对的肾细胞癌和相邻健康肾组织标本中 AdipoR1 和 AdipoR2 的表达情况。我们还通过实时聚合酶链反应研究了 45 例肾细胞癌的 mRNA 表达情况。最后，我们利用 Western blot 证实了脂联素受体的存在，并随后在肾癌细胞系 786-O 中研究了脂联素的细胞信号通路。与肥胖相关的癌症比与肥胖无关的癌症更有可能表达 AdipoR1。在与肥胖密切相关的肾细胞癌标本中，93.8%表达 AdipoR1，而与肥胖无关的宫颈细胞癌标本中，44.9%表达 AdipoR1（p<0.001）。恶性和良性肾组织标本中脂联素受体的表达或其 mRNA 无差异。总体而言，脂联素受体或其 mRNA 的表达与肿瘤预后因素之间没有相关性。最后，Western blot 证实了肾癌细胞系 786-O 中 AdipoR1 的存在，脂联素在该细胞系中激活了几种体外信号通路。总之，我们首次报道了上述癌症中 AdipoR1 和 AdipoR2 的表达情况，并且 AdipoR1 在肥胖相关的癌症中更为普遍表达。
