PMID- 17615358
OWN - NLM
STAT- MEDLINE
DCOM- 20070725
LR  - 20220606
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 317
IP  - 5834
DP  - 2007 Jul 6
TI  - Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 
      production.
PG  - 121-4
AB  - 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.
FAU - Naugler, Willscott E
AU  - Naugler WE
AD  - Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology 
      and Cancer Center, University of California, San Diego, CA 93093, USA.
FAU - Sakurai, Toshiharu
AU  - Sakurai T
FAU - Kim, Sunhwa
AU  - Kim S
FAU - Maeda, Shin
AU  - Maeda S
FAU - Kim, Kyounghyun
AU  - Kim K
FAU - Elsharkawy, Ahmed M
AU  - Elsharkawy AM
FAU - Karin, Michael
AU  - Karin M
LA  - eng
GR  - T32 CA121938/CA/NCI NIH HHS/United States
GR  - CA118165/CA/NCI NIH HHS/United States
GR  - ES006376/ES/NIEHS NIH HHS/United States
GR  - ES004151/ES/NIEHS NIH HHS/United States
GR  - T32 DK007202/DK/NIDDK NIH HHS/United States
GR  - R01 CA118165/CA/NCI NIH HHS/United States
GR  - DK007202/DK/NIDDK NIH HHS/United States
GR  - R01 ES006376/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Interleukin-6)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (RNA, Messenger)
RN  - 3IQ78TTX1A (Diethylnitrosamine)
RN  - 4TI98Z838E (Estradiol)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
EIN - Science. 2009 Dec 4;326(5958):1346
CIN - Science. 2007 Jul 6;317(5834):51-2. PMID: 17615328
CIN - Science. 2007 Nov 23;318(5854):1239-40; author reply 1239-40. PMID: 18033865
MH  - Animals
MH  - Carbon Tetrachloride/administration & dosage
MH  - Diethylnitrosamine/administration & dosage/metabolism
MH  - Estradiol/pharmacology
MH  - Female
MH  - Hepatocytes
MH  - Interleukin-6/blood/genetics/*metabolism
MH  - Kupffer Cells/*metabolism
MH  - Liver/metabolism/pathology
MH  - Liver Neoplasms, Experimental/chemically induced/immunology/*physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/*physiology
MH  - Necrosis
MH  - Ovariectomy
MH  - RNA, Messenger/genetics/metabolism
MH  - *Sex Characteristics
EDAT- 2007/07/07 09:00
MHDA- 2007/07/26 09:00
CRDT- 2007/07/07 09:00
PHST- 2007/07/07 09:00 [pubmed]
PHST- 2007/07/26 09:00 [medline]
PHST- 2007/07/07 09:00 [entrez]
AID - 317/5834/121 [pii]
AID - 10.1126/science.1140485 [doi]
PST - ppublish
SO  - Science. 2007 Jul 6;317(5834):121-4. doi: 10.1126/science.1140485.