Nuclear localization of epidermal growth factor receptor (EGFR) in ameloblastomas

Oncotarget. 2015;6(12):9679-85. doi: 10.18632/oncotarget.3919.

Abstract

Background: Ameloblastoma is a locally invasive neoplasm often associated with morbidity and facial deformities, showing increased Epidermal Growth Factor Receptor (EGFR) expression. Inhibition of EGFR was suggested as a treatment option for a subset of ameloblastomas. However, there are resistance mechanisms that impair anti-EGFR therapies. One important resistance mechanism for EGFR-inhibition is the EGFR nuclear localization, which activates genes responsible for its mitogenic effects, such as Cyclin D1.

Methods: We assessed EGFR nuclear localization in encapsulated (unicystic, n = 3) and infiltrative (multicystic, n = 11) ameloblastomas and its colocalization with Cyclin D1 by using anti-EGFR and anti-lamin B1 double labeling immunofluorescence analyzed by confocal microscopy. Oral inflammatory fibrous hyperplasia and oral squamous cell carcinoma samples were used for comparison.

Results: Twelve cases of ameloblastoma exhibited nuclear EGFR colocalization with lamin B1. This positive staining was mainly observed in the ameloblast-like cells. The EGFR nuclear localization was also observed in control samples. In addition, nuclear EGFR colocalized with Cyclin D1 in ameloblastomas.

Conclusions: Nuclear EGFR occurs in ameloblastomas in association with Cyclin D1 expression, which is important in terms of tumor biology clarification and raises a concern about anti-EGFR treatment resistance in ameloblastomas.

Keywords: cyclin D1; epidermal growth factor receptor; nuclear EGFR; odontogenic tumors; pathology; therapy resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ameloblastoma / metabolism*
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / metabolism
  • Cell Nucleus / metabolism*
  • Cyclin D1 / metabolism
  • ErbB Receptors / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inflammation
  • Jaw Neoplasms / metabolism*
  • Lamin Type B / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Mouth Neoplasms / metabolism

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • Lamin Type B
  • Cyclin D1
  • EGFR protein, human
  • ErbB Receptors