Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors

Expert Opin Ther Targets. 2017 Jan;21(1):77-89. doi: 10.1080/14728222.2017.1257000. Epub 2016 Nov 18.

Abstract

Four members of the PAX family, PAX2, PAX4, PAX6 and PAX8 are known to be expressed in the pancreas. Accumulated evidences indicate that several pancreatic expressed PAX genes play a significant role in pancreatic development/functionality and alterations in these genes are involved in the pathogenesis of pancreatic diseases. Areas covered: In this review, we summarize the ongoing research related to pancreatic PAX genes in diabetes mellitus and pancreatic neuroendocrine tumors. We dissect the current knowledge at different levels; from mechanistic studies in cell lines performed to understand the molecular processes controlled by pancreatic PAX genes, to in vivo studies using rodent models that over-express or lack specific PAX genes. Finally, we describe human studies associating variants on pancreatic-expressed PAX genes with pancreatic diseases. Expert opinion: Based on the current literature, we propose that future interventions to treat pancreatic neuroendocrine tumors and diabetes mellitus could be developed via the modulation of PAX4 and/or PAX6 regulated pathways.

Keywords: Diabetes mellitus; PAX genes; PAX2; PAX4; PAX6; PAX8; pancreatic neuroendocrine tumors.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Line
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / physiopathology
  • Diabetes Mellitus / therapy
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / therapy
  • Paired Box Transcription Factors / genetics*
  • Pancreas / physiopathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy

Substances

  • Paired Box Transcription Factors