Journal
ONCOTARGET
Volume 6, Issue 12, Pages 9679-9685Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3919
Keywords
odontogenic tumors; cyclin D1; epidermal growth factor receptor; nuclear EGFR; therapy resistance
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)/Brazil
- Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)/Brazil
- National Institutes of Health/USA (NIH) [1R03TW008709]
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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.
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