Diabetes and oral oncogenesis.
Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in humans including type I diabetic and normal rats. Tobacco and alcohol, as well as dysregulation of oncogenes and tumor suppressor genes, epigenetic changes and mitochondrial mutations have been implicated in OSCC development. Recent epidemiological studies have incriminated diabetes mellitus as a risk factor for the development of OSCC, as well as oral premalignant lesions. Recently, an animal model was employed to study the influence of diabetes on signal transduction pathways in every stage of oral cancer development, from normal mucosa to hyperplasia, dysplasia, early invasion, well differentiated OSCC and moderately differentiated OSCC. Diabetes was induced by streptozotocin and chemical carcinogenesis was induced by the carcinogen 4-nitroquinoline N-oxide. The expression of EGFR, erbB2, erbB3, FGFR-2, FGFR-3, c-myc, N-ras, ets-1, H-ras, c-fos and c-jun, the tumor suppressor genes p53 and p16, apoptosis markers Bax and Bcl-2, and the cell proliferation marker Ki-67 in the sequential stages of rat oral oncogenesis was investigated. Diabetes seems to promote the activation of the Ras/Raf/MAPK signal transduction pathway mainly by induction of erbB2 and erbB3 receptors, leading to increased cell proliferation, while there was no difference in apoptosis levels during oncogenesis.
Vairaktaris
Eleftherios
E
Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Kifissias and Perikleous Stavrou 9, Athens 11524, Greece. lvairakt@med.uoa.gr
Spyridonidou
Sofia
S
Goutzanis
Lambros
L
Vylliotis
Antonis
A
Lazaris
Andreas
A
Donta
Ismini
I
Perrea
Despina
D
Yapijakis
Christos
C
Patsouris
Efstratios
E
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D009062:Mouth Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology