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

被引:12
|
作者
Pereira, Nubia Braga [1 ]
de Melo do Carmo, Ana Carolina [1 ]
Diniz, Marina Goncalves [2 ]
Gomez, Ricardo Santiago [2 ]
Gomes, Dawidson Assis [3 ]
Gomes, Carolina Cavalieri [1 ]
机构
[1] Univ Fed Minas Gerais, Dept Pathol, Inst Biol Sci, Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Sch Dent, Dept Oral Surg & Pathol, Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG, Brazil
基金
美国国家卫生研究院;
关键词
odontogenic tumors; cyclin D1; epidermal growth factor receptor; nuclear EGFR; therapy resistance; ACQUIRED-RESISTANCE; PROGNOSTIC VALUE; BREAST-CANCER; EXPRESSION; MECHANISMS; INHIBITORS; THERAPIES; CYCLIN-D1; PATHWAY; TARGET;
D O I
10.18632/oncotarget.3919
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:9679 / 9685
页数:7
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