Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Cell. 2010 Jan 22;140(2):197-208. doi: 10.1016/j.cell.2009.12.052.
Epidemiological studies indicate that overweight and obesity are associated with increased cancer risk. To study how obesity augments cancer risk and development, we focused on hepatocellular carcinoma (HCC), the common form of liver cancer whose occurrence and progression are the most strongly affected by obesity among all cancers. We now demonstrate that either dietary or genetic obesity is a potent bona fide liver tumor promoter in mice. Obesity-promoted HCC development was dependent on enhanced production of the tumor-promoting cytokines IL-6 and TNF, which cause hepatic inflammation and activation of the oncogenic transcription factor STAT3. The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers.
流行病学研究表明，超重和肥胖与癌症风险增加有关。为了研究肥胖如何增加癌症风险和发展，我们专注于肝细胞癌（HCC），这是最常见的肝癌形式，其发生和发展受肥胖的影响在所有癌症中是最强的。我们现在证明，饮食或遗传肥胖是小鼠中一种有效的真正的肝脏肿瘤促进剂。肥胖促进 HCC 的发展依赖于肿瘤促进细胞因子 IL-6 和 TNF 的增强产生，其导致肝脏炎症和致癌转录因子 STAT3 的激活。肥胖引起的慢性炎症反应和 IL-6 和 TNF 的增强产生也可能增加其他癌症的风险。
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