Publication: Diabetes enhances the expression of H-ras and suppresses the expression of EGFR leading to increased cell proliferation
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Date
2009
Authors
Vairaktaris, Eleftherios ; Goutzanis, Lampros ; Yapijakis, Christos ; Vassiliou, Stavros ; Spyridonidou, Sofia ; Vylliotis, Antonis ; Nkenke, Emeka ; Lazaris, A. Ch. ; Strantzias, Pashalis ; Patsouris, Efstratios
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
EGFR kinase activity triggers numerous
signaling pathways, such as the Ras/Raf/MAPK cascade,
leading to the activation of various mitogen activated
protein kinases, which are implicated in cell proliferation
through induction of several genes, including c-fos. The
possible effect of diabetes on the expression of the
oncogenes EGFR, H-ras and c-fos was investigated in an
experimental model of chemically induced oral
oncogenesis in normal and diabetic (type I) Sprague-
Dawley rats. Thirteen diabetic and twelve normal rats
developed cancer after 4NQO treatment, while six
diabetic and six normal animals were used as controls.
The biopsies were classified pathologically (ranging
from dysplasia to moderately differentiated oral
squamous cell carcinoma) and were studied
immunohistochemically. Several representative
histological regions from each biopsy were analysed in
regard to EGFR, H-ras and c-fos expression, and a
comparison between normal and diabetic rats was
effected. A trend of decreased EGFR expression in
diabetic compared to normal rats was revealed
throughout oncogenesis, which was significant in the
stage of dysplasia (P<0.05). On the contrary, a trend of
increased H-ras expression was observed in diabetic compared to normal rats during oncogenesis, which rose
significantly in early invasion and well differentiated
OSCC (P<0.001 and P<0.01 respectively). Finally, no
statistical differences concerning c-fos expression were
detected between diabetic and normal animals. In
conclusion, it seems that diabetes reduces the expression of EGFR and initiates the Ras/Raf/MAPK signal
transduction pathway by enhancing activation of other
signalling molecules, such as the diabetes-associated
Insulin Receptor Substrate-1, leading to increased cell
proliferation without c-fos involvement.
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