Bladder Cancer
Section: Section of Molecular Carcinogenesis
The most common bladder cancer in Western societies are called translational cell carcinomas. Around 70-80% of transitional cell carcinomas of the bladder present as superficial non-muscle invasive papillary carcinomas (pTa or pT1) that are associated with a high risk of recurrence (70%) following treatment, but low risk (10-20%) of progression to muscle invasion. The remaining 20-30% of bladder cancers show muscle invasion at the time of diagnosis (>T2), have no association with papillary tumours, and are thought to arise from carcinomas in situ (CIS). Clinically new molecular markers are urgently required (i) to identify those early stage tumours that progress and become life threatening and (ii) to identify those tumours that will respond to therapy.
Amplification and overexpression of E2F3 in human bladder cancer
Investigators: A Feber, J Clark, G Goodwin, PH Smith, A Fletcher, S Edwards, P Flohr, A Falconer, T Roe, N Dennis, C Fisher, R Wooster, R Huddart, CS Cooper; in collaboration with CS Foster, AR Dodson, University of Liverpool and G Kovacs at the University of Heidelberg
External Funding: Cancer Research UK
We have demonstrated that, in human bladder cancer, amplification of the E2F3 gene, located at 6p22, is associated with overexpression of its encoded mRNA transcripts and high levels of expression of E2F3 protein. Immunohistochemical analyses of E2F3 protein levels have established that around one-third (33/101) of primary transitional cell carcinomas of the bladder overexpress nuclear E2F3 protein, with the proportion of tumours containing overexpressed nuclear E2F3 increasing with tumour stage and grade. When considered together with the established role of E2F3 in cell cycle progression, these results suggest that the E2F3 gene represents a candidate bladder cancer oncogene that is activated by DNA amplification and overexpression.
In the Section of Molecular Carcinogenesis
