PMID- 30469530
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 10
IP  - 12
DP  - 2018 Nov 22
TI  - mTOR Activation in Liver Tumors Is Associated with Metabolic Syndrome and 
      Non-Alcoholic Steatohepatitis in Both Mouse Models and Humans.
LID - 10.3390/cancers10120465 [doi]
LID - 465
AB  - Non-alcoholic steatohepatitis (NASH) can cause liver fibrosis and cirrhosis, with 
      final progression to hepatocellular carcinoma (HCC) in some cases. Various 
      factors have been suggested to be involved in the development of NASH. 
      Considering the many possible contributing factors, we postulated that mechanisms 
      of progression from NASH to HCC could differ depending on the risk factors. In 
      the present study, we applied two mouse models of NASH(-)HCC and performed 
      histopathological and proteome analyses of mouse liver tumors. Furthermore, to 
      compare the mechanisms of NASH(-)HCC progression in mice and humans, we 
      investigated HCCs in humans with a background of metabolic syndrome and NASH, as 
      well as HCCs associated with hepatitis virus infection by immunohistochemistry. 
      It was demonstrated that upstream regulators associated with the mammalian target 
      of rapamycin (mTOR) pathway were altered in liver tumors of mice with metabolic 
      syndrome characteristics (TSOD mice) using proteome analysis. Immunohistochemical 
      analysis showed that mTOR was characteristically phosphorylated in liver tumors 
      of TSOD mice and HCCs from metabolic syndrome cases in humans. These results 
      indicated that the mTOR pathway is characteristically activated in liver tumors 
      with metabolic syndrome and NASH, unlike liver tumors with other etiologies.
FAU - Okuno, Takahiro
AU  - Okuno T
AD  - Department of Molecular Pathology, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan. 
      m2026860@med.osaka-cu.ac.jp.
FAU - Kakehashi, Anna
AU  - Kakehashi A
AUID- ORCID: 0000-0003-1149-1450
AD  - Department of Molecular Pathology, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan. 
      anna@med.osaka-cu.ac.jp.
FAU - Ishii, Naomi
AU  - Ishii N
AD  - Department of Molecular Pathology, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan. 
      m1159070@med.osaka-cu.ac.jp.
FAU - Fujioka, Masaki
AU  - Fujioka M
AUID- ORCID: 0000-0003-0048-2874
AD  - Department of Molecular Pathology, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan. 
      m2066048@med.osaka-cu.ac.jp.
FAU - Gi, Min
AU  - Gi M
AD  - Department of Molecular Pathology, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan. 
      mwei@med.osaka-cu.ac.jp.
FAU - Wanibuchi, Hideki
AU  - Wanibuchi H
AD  - Department of Molecular Pathology, Osaka City University Graduate School of 
      Medicine, Asahi-machi 1-4-3, Abeno-ku, Osaka 545-8585, Japan. 
      wani@med.osaka-cu.ac.jp.
LA  - eng
GR  - 15K18415/Ministry of Health, Labor and Welfare of Japan and the Japan Science and 
      Technology Corporation/
PT  - Journal Article
DEP - 20181122
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6315895
OTO - NOTNLM
OT  - NASH
OT  - hepatocellular carcinoma
OT  - mTOR
OT  - metabolic syndrome
OT  - mouse models
COIS- The authors declare no conflict of interest.
EDAT- 2018/11/25 06:00
MHDA- 2018/11/25 06:01
PMCR- 2018/11/22
CRDT- 2018/11/25 06:00
PHST- 2018/10/16 00:00 [received]
PHST- 2018/11/12 00:00 [revised]
PHST- 2018/11/20 00:00 [accepted]
PHST- 2018/11/25 06:00 [entrez]
PHST- 2018/11/25 06:00 [pubmed]
PHST- 2018/11/25 06:01 [medline]
PHST- 2018/11/22 00:00 [pmc-release]
AID - cancers10120465 [pii]
AID - cancers-10-00465 [pii]
AID - 10.3390/cancers10120465 [doi]
PST - epublish
SO  - Cancers (Basel). 2018 Nov 22;10(12):465. doi: 10.3390/cancers10120465.