Understanding the Tumor Suppressor PTEN in Chronic Alcoholism and Hepatocellular Carcinoma

  • Colin T. ShearnEmail author
  • Dennis R. Petersen
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 815)


The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatidylinositol (PtdIns) phosphatase that regulates Akt activation via PtdIns 3 kinase. Changes in PTEN expression and/or activity have been identified in a variety of chronic hepatocellular disorders including obesity, NAFLD, NASH, and alcoholism. In cancer biology, PTEN is frequently mutated or deleted in a wide variety of tumors. Mutations, decreased promoter activity, and decreased expression in PTEN are frequently identified in patients with hepatocellular carcinoma. While the majority of research on PTEN concerns obesity and NASH, PTEN clearly has a role in hepatic insulin sensitivity and in the development of steatosis during chronic alcoholism. Yet, in chronic alcoholics and HCC, very little is known concerning PTEN mutation/deletion or low PTEN expression. This review is focused on an overview of the current knowledge on molecular mechanisms of dysregulation of PTEN expression/activity in the liver and their relationship to development of ethanol-induced hepatocellular damage and cancer.


PTEN Chronic ethanol Fatty acid synthesis Posttranslational modification Oxidative stress Hepatic steatosis 


Grants and Funding

This research was funded by the following grants from the National Institutes of Health; 5F32AA018613-03 CTS.


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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesUniversity of Colorado Denver Anchutz Medical CampusAuroraUSA

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