Interaction between fatty acid synthase and human epidermal growth receptor 2 (HER2) in osteosarcoma cells

Int J Clin Exp Pathol. 2014 Dec 1;7(12):8777-83. eCollection 2014.

Abstract

Elevated expression of fatty acid synthase (FASN) and human epidermal growth factor receptor-2 (HER2) are observed in human osteosarcoma (OS). The aim in this study is to investigate a possible connection between FASN expression and the activity of HER2. The immunohistochemistry staining was conducted on 24 OS specimens from patients, which revealed a significant positive correlation between FASN and HER2 as well as p-HER2 protein expression. Furthermore, the human OS cell lines MG-63 and U2-OS were treated with FASN-specific RNAi Plasmid or Lapatinib (an inhibitor of HER2). The mRNA of HER2 and FASN was measured using RT-PCR. Western blot was performed to detect the protein expression of HER2, p-HER2 and FASN. The results demonstrated that HER2 modulates FASN expression, inhibition of FASN resulted in down-regulation of HER2 and p-HER2 protein in OS cells. Our findings suggested that there was positive feedback regulation between FASN and HER2 expression and phosphorylation in OS cells.

Keywords: FASN; HER2; Osteosarcoma; positive feedback regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Fatty Acid Synthase, Type I / metabolism*
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Immunohistochemistry
  • Osteosarcoma / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptor, ErbB-2 / metabolism*

Substances

  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • ERBB2 protein, human
  • Receptor, ErbB-2