Your browser doesn't support javascript.
loading
Loss of Thymine DNA Glycosylase Causes Dysregulation of Bile Acid Homeostasis and Hepatocellular Carcinoma.
Hassan, Haider M; Isovic, Majdina; Kolendowski, Bart; Bauer-Maison, Natasha; Onabote, Oladapo; Cecchini, Matthew; Haig, Aaron; Maleki Vareki, Saman; Underhill, T Michael; Torchia, Joseph.
Afiliação
  • Hassan HM; Department of Biochemistry, Western University, London, ON, Canada; Department of Oncology, The London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London Health Science Centre, London, ON, Canada.
  • Isovic M; Department of Oncology, The London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London Health Science Centre, London, ON, Canada.
  • Kolendowski B; Department of Biochemistry, Western University, London, ON, Canada; Department of Oncology, The London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London Health Science Centre, London, ON, Canada.
  • Bauer-Maison N; Department of Pathology and Laboratory Medicine, London Health Science Centre, London, ON, Canada.
  • Onabote O; Department of Biochemistry, Western University, London, ON, Canada; Department of Oncology, The London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London Health Science Centre, London, ON, Canada.
  • Cecchini M; Department of Pathology and Laboratory Medicine, London Health Science Centre, London, ON, Canada.
  • Haig A; Department of Pathology and Laboratory Medicine, London Health Science Centre, London, ON, Canada.
  • Maleki Vareki S; Department of Oncology, The London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London Health Science Centre, London, ON, Canada; Department of Interdisciplinary Medical Sciences, London Health Science Centre, London, ON, Canada; Department of Pathology and Laborato
  • Underhill TM; Department of Cellular and Physiological Sciences and the Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.
  • Torchia J; Department of Biochemistry, Western University, London, ON, Canada; Department of Oncology, The London Regional Cancer Program, London, ON, Canada; Lawson Health Research Institute, London Health Science Centre, London, ON, Canada. Electronic address: jtorchia@uwo.ca.
Cell Rep ; 31(1): 107475, 2020 04 07.
Article em En | MEDLINE | ID: mdl-32268085
Thymine DNA glycosylase (TDG) is a nuclear receptor coactivator that plays an essential role in the maintenance of epigenetic stability in cells. Here, we demonstrate that the conditional deletion of TDG in adult mice results in a male-predominant onset of hepatocellular carcinoma (HCC). TDG loss leads to a prediabetic state, as well as bile acid (BA) accumulation in the liver and serum of male mice. Consistent with these data, TDG deletion led to dysregulation of the farnesoid X receptor (FXR) and small heterodimer partner (SHP) regulatory cascade in the liver. FXR and SHP are tumor suppressors of HCC and play an essential role in BA and glucose homeostasis. These results indicate that TDG functions as a tumor suppressor of HCC by regulating a transcriptional program that protects against the development of glucose intolerance and BA accumulation in the liver.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos e Sais Biliares / Carcinoma Hepatocelular / Timina DNA Glicosilase Tipo de estudo: Etiology_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácidos e Sais Biliares / Carcinoma Hepatocelular / Timina DNA Glicosilase Tipo de estudo: Etiology_studies Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2020 Tipo de documento: Article