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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
来源:
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.
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页码:9679 / 9685
页数:7
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