STUDY OF THE IMPACT OF DNA METHYLATION ON THE EXPRESSION OF CELL CYCLE REGULATORS IN BLADDER CARCINOMA

Mohamed Abd–Ellatif; Raymonde H. Assaf; Fagr B. El–Shahat; Ahmed B. Shehab El–Din; Salwa M. Abou El–Khair

Volume : V, Issue : V, May - 2015

STUDY OF THE IMPACT OF DNA METHYLATION ON THE EXPRESSION OF CELL CYCLE REGULATORS IN BLADDER CARCINOMA

Mohamed Abd Ellatif, Raymonde H. Assaf, Fagr B. El Shahat, Ahmed B. Shehab El Din, Salwa M. Abou El Khair

Abstract :

&nbsp;The aim of this work is to evaluate the DNA methylation status and expression of different cell cycle regulators during multistage carcinogenesis of rat urinary bladder. Materials and Methods: This experimental&nbsp; study included 64 male (fisher 344) rats (6 weeks old). They were divided into experimental group (n= 48) and control&nbsp; group (n= 16). Urinary bladder carcinogenesis was induced in rats of the experimental group by N&ndash;Ethyl N&ndash;Butane Nitrosamine (EBN) in their drinking water for 10 weeks. At the 10th, 14th, 20th, and 24th week from the time of induction&nbsp; of carcinogenesis, rats were sacrificed. Pathological and normal urinary bladder tissue specimens from experimental&nbsp; and control rats were excised and divided into 3 samples to be used for histopathological analysis, the expression of&nbsp; both cyclin D1 and E, and for methylation changes. The results of our study showed that the expression of both cyclin&nbsp; D1 and cyclin E were very highly significantly increased in hyperplasia, dysplasia, and carcinoma compared with the&nbsp; control group. There was a gradual methylation changes during urinary bladder carcinogenesis. Conclusion: Multiple&nbsp; stepwise progressive changes in methylation patterns are observed during EBN induced rat urinary bladder carcinogenesis. These methylation changes occur early during oncogenesis and are detectable prior to the appearance of clinically evident tumor. Overexpression of cyclin D1 and cyclin E is an important and frequent molecular event, at relatively&nbsp; early stage during the development of urinary bladder cancer. Both cyclin D1 and E could become useful biomarkers&nbsp; to identify precancerous lesions in the early stage of urinary bladder cancer.