Hepatocellular carcinoma, a common and deadly cancer of the liver, is 3 to 5 times more likely to occur in men than in women (see the Perspective by Lawrence et al.). Working in a mouse model in which liver cancer is induced by exposure to a chemical carcinogen, Naugler et al. propose a molecular basis for this phenomenon, explained by the action of the female hormone estrogen and its ability to inhibit inflammatory responses in the liver. Estrogen acts to inhibit secretion of interleukin-6 (IL-6) by liver macrophages known as Kupffer cells. Production of IL-6 was dependent on the signaling adaptor protein MyD88, which in turn may be activated by products of dying cells in the injured liver. Rakoff-Nahoum and Medzhitov implicate MyD88 in promoting another cancer, that of the intestine. Inflammation is known to be a risk factor for colorectal tumors. In a mouse model of intestinal tumorigenesis, mice lacking MyD88 showed inhibited growth and progression of tumors.
W. E. Naugler, T. Sakurai, S. Kim, S. Maeda, K. Kim, A. M. Elsharkawy, M. Karin, Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317, 121-124 (2007). [Abstract] [Full Text]