The inhibition of nitric oxide production induces bladder tumour protein profile modification

LANGLE Y; BELGOROSKY D ; MONGE M ; COLOMÉ N; ROJAS BILBAO E; MARINO L ; MALAGRINO H; PASIK L; CASABÉ A; REVENTOS J; CANALS F; EIJÁN AM

Barcelona

Congreso; Time to Imagine, 5th Congress of the Spanish Proteomics Society, Barcelona, Spain; 2013

Spanish Proteomics Society

MODIFICATION OF THE PROTEIN PROFILE OF BLADDER TUMOURS INDUCED BY THE INHIBITION OF NITRIC OXIDE PRODUCTION Langle Y[1], Belgorosky D[1], Monge M[2,3], Colomé N[2], Rojas Bilbao E[1], Marino L[1], Malagrino H[1], Pasik L[1], Casabé A[1], Reventos J[2],Canals F[2] & Eiján AM[1] [1] Ángel H. Roffo Institute of Oncology, CABA, Argentina [2] Vall Hebron Institute of Oncology, VHIO, Barcelona, Spain [3] martamonge@hotmail.com Bladder cancer (BC) is the second cause of death from male urogenital tract tumours. It is classified as non invasive (NMI) or muscle invasive, when it reaches the detrusor muscle. NMI tumours represent 80% of diagnosed BC and the transurethral resection can be useful to eliminate the tumour when there is only one injury and the surrounding tissue is histologically normal. However, recurrences appear in 50% of patients, and 30% of them present a more invasive pattern, requiring more aggressive therapies. The identification of new players involved in tumour progression can provide new therapeutic targets. Nitric oxide (NO) is a free radical produced by NO synthase (NOS). We previously described that 50% of human BC express the inducible isoform iNOS. We determined that 80% of iNOS+ patients show tumoral recurrence in the first year after the treatment while only 20% of iNOS- patients show recurrence during that time. We also demonstrated that mouse MB49 BC growth is reduced with L-NAME (inhibitor of NO production) therapy. These results led us to propose that modulation of NO production in iNOS+ tumour could be a useful therapeutic strategy. The aim of this work was to evaluate mouse MB49 BC protein expression and the modification of its protein profile upon L-NAME treatment. MB49 bladder tumours derived from mice treated or not with L-NAME were compared by 2D-DIGE technology. A total of 52 proteins were identified as differentially expressed. L-NAME induces the over-expression of Ras suppressor protein1 (fold change 1.66; p