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NCOA5 haploinsufficiency results in glucose intolerance and subsequent hepatocellular carcinoma.
- Source :
-
Cancer cell [Cancer Cell] 2013 Dec 09; Vol. 24 (6), pp. 725-37. - Publication Year :
- 2013
-
Abstract
- Type 2 diabetes (T2D) and male gender are associated with hepatocellular carcinoma (HCC) development. We demonstrate that heterozygous deletion of the Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor development is preceded by increased interleukin-6 (IL-6) expression, early-onset glucose intolerance, and progressive steatosis and dysplasia in livers. Blockading IL-6 overexpression averts glucose intolerance and partially deters HCC development. Moreover, reduced NCOA5 expression is associated with a fraction of human HCCs and HCCs with comorbid T2D. These findings suggest that NCOA5 is a haploinsufficient tumor suppressor and that NCOA5 deficiency increases susceptibility to both glucose intolerance and HCC, partially by increasing IL-6 expression. Thus, our findings open additional avenues for developing therapeutic approaches to combat these diseases.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Animals
Fatty Liver etiology
Female
Humans
Interleukin-6 genetics
Interleukin-6 physiology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Middle Aged
Promoter Regions, Genetic
Receptors, Androgen genetics
STAT3 Transcription Factor physiology
Carcinoma, Hepatocellular etiology
Glucose Intolerance etiology
Haploinsufficiency
Liver Neoplasms etiology
Nuclear Receptor Coactivators genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 24
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 24332041
- Full Text :
- https://doi.org/10.1016/j.ccr.2013.11.005