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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-3-13
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1699-5848
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
531-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Diabetes enhances the expression of H-ras and suppresses the expression of EGFR leading to increased cell proliferation.
pubmed:affiliation
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Athens, Greece. lvairakt@med.uoa.gr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't