Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production - PubMed (original) (raw)
. 2007 Jul 6;317(5834):121-4.
doi: 10.1126/science.1140485.
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- PMID: 17615358
- DOI: 10.1126/science.1140485
Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production
Willscott E Naugler et al. Science. 2007.
Erratum in
- Science. 2009 Dec 4;326(5958):1346
Abstract
Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.
Comment in
- Cancer. Sex, cytokines, and cancer.
Lawrence T, Hageman T, Balkwill F. Lawrence T, et al. Science. 2007 Jul 6;317(5834):51-2. doi: 10.1126/science.1146052. Science. 2007. PMID: 17615328 No abstract available. - Estrogen and tumors: for better or for worse?
van der Windt DJ, Kok NF, Ijzermans J. van der Windt DJ, et al. Science. 2007 Nov 23;318(5854):1239-40; author reply 1239-40. doi: 10.1126/science.318.5854.1239c. Science. 2007. PMID: 18033865 No abstract available.
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- DK007202/DK/NIDDK NIH HHS/United States
- R01 ES006376/ES/NIEHS NIH HHS/United States
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