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

Pereira NB, do Carmo AC, Diniz MG, Gomez RS, Gomes DA, Gomes CC - Oncotarget (2015)

Bottom Line: However, there are resistance mechanisms that impair anti-EGFR therapies.Oral inflammatory fibrous hyperplasia and oral squamous cell carcinoma samples were used for comparison.This positive staining was mainly observed in the ameloblast-like cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus

The nuclear EGFR co-localizes with Cyclin D1 positive cellsThe co-localization was observed using specific antibodies for the EGFR (red) and Cyclin D1 (green). Nuclear staining with DAPI is shown in blue. Serial optical sections were collected for three-dimensional reconstruction; x-z sections are shown at the top and y-z sections are shown on the right, to confirm nuclear co-localization of EGFR with Cyclin D1. Original magnification: 63x.
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Figure 5: The nuclear EGFR co-localizes with Cyclin D1 positive cellsThe co-localization was observed using specific antibodies for the EGFR (red) and Cyclin D1 (green). Nuclear staining with DAPI is shown in blue. Serial optical sections were collected for three-dimensional reconstruction; x-z sections are shown at the top and y-z sections are shown on the right, to confirm nuclear co-localization of EGFR with Cyclin D1. Original magnification: 63x.

Mentions: Additionally, we evaluated if nuclear EGFR co-localizes with Cyclin D1 positive cells. We found that Cyclin D1 is co-localized with EGFR in unicystic and multicystic ameloblastomas, and the co-localization is clearer in the periphery of epithelial islands (ameloblast-like cells), which are cells that proliferate more (Figures 4 and 5). The location of the EGFR in the nucleus was schematically shown in Figure 6.


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

Pereira NB, do Carmo AC, Diniz MG, Gomez RS, Gomes DA, Gomes CC - Oncotarget (2015)

The nuclear EGFR co-localizes with Cyclin D1 positive cellsThe co-localization was observed using specific antibodies for the EGFR (red) and Cyclin D1 (green). Nuclear staining with DAPI is shown in blue. Serial optical sections were collected for three-dimensional reconstruction; x-z sections are shown at the top and y-z sections are shown on the right, to confirm nuclear co-localization of EGFR with Cyclin D1. Original magnification: 63x.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496389&req=5

Figure 5: The nuclear EGFR co-localizes with Cyclin D1 positive cellsThe co-localization was observed using specific antibodies for the EGFR (red) and Cyclin D1 (green). Nuclear staining with DAPI is shown in blue. Serial optical sections were collected for three-dimensional reconstruction; x-z sections are shown at the top and y-z sections are shown on the right, to confirm nuclear co-localization of EGFR with Cyclin D1. Original magnification: 63x.
Mentions: Additionally, we evaluated if nuclear EGFR co-localizes with Cyclin D1 positive cells. We found that Cyclin D1 is co-localized with EGFR in unicystic and multicystic ameloblastomas, and the co-localization is clearer in the periphery of epithelial islands (ameloblast-like cells), which are cells that proliferate more (Figures 4 and 5). The location of the EGFR in the nucleus was schematically shown in Figure 6.

Bottom Line: However, there are resistance mechanisms that impair anti-EGFR therapies.Oral inflammatory fibrous hyperplasia and oral squamous cell carcinoma samples were used for comparison.This positive staining was mainly observed in the ameloblast-like cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

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.

No MeSH data available.


Related in: MedlinePlus