GFRα2 prompts cell growth and chemoresistance through down-regulating tumor suppressor gene PTEN via Mir-17-5p in pancreatic cancer

Cancer Lett. 2016 Oct 1;380(2):434-441. doi: 10.1016/j.canlet.2016.06.016. Epub 2016 Jul 8.

Abstract

Nerve growth factors and their receptors have received an increasing attention in certain cancers since they play an important role in regulating tumorigenesis, biological process and metastasis. Here we aimed at characterizing a new function of one of the subtypes of growth factor receptors (GFR), GFRα2, in pancreatic cancer. In this study, we showed that GFRα2 was up-regulated in pancreatic adenocarcinoma and was positively correlated with tumor size and perineural invasion, which indicated that it may be associated with cell growth and apoptosis. Mechanically, we discovered that high GFRα2 expression level leads to PTEN inactivation via enhancing Mir-17-5p level.

Keywords: Chemoresistance; GFRα2; Mir-17-5p; PTEN; Pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / enzymology*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Drug Resistance, Neoplasm*
  • Female
  • Gemcitabine
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / genetics
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • RNA Interference
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden

Substances

  • GFRA2 protein, human
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • MIRN17 microRNA, human
  • MicroRNAs
  • Deoxycytidine
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Gemcitabine