Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

Int J Oral Sci. 2013 Mar;5(1):14-20. doi: 10.1038/ijos.2013.10. Epub 2013 Mar 15.

Abstract

In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amphiregulin
  • Betacellulin
  • EGF Family of Proteins
  • Epidermal Growth Factor / metabolism
  • Epiregulin
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Profiling
  • Glycoproteins / metabolism
  • Heparin / metabolism
  • Heparin-binding EGF-like Growth Factor
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keratinocytes / metabolism
  • Leukoplakia, Oral / metabolism*
  • Lichen Planus, Oral / metabolism
  • Ligands
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism
  • Nerve Growth Factors
  • Neuregulins / metabolism
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3 / metabolism
  • Receptor, ErbB-4
  • Receptors, Cell Surface / metabolism
  • Transforming Growth Factor alpha / metabolism
  • Up-Regulation / physiology*

Substances

  • AREG protein, human
  • Amphiregulin
  • BTC protein, human
  • Betacellulin
  • EGF Family of Proteins
  • EREG protein, human
  • Epiregulin
  • Glycoproteins
  • HBEGF protein, human
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • NRG2 protein, human
  • Nerve Growth Factors
  • Neuregulins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Transforming Growth Factor alpha
  • neuregulin-4
  • Epidermal Growth Factor
  • Heparin
  • ERBB2 protein, human
  • ERBB3 protein, human
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4