Bladder cancer: tumor progression is associated with adherin switch and beta-catenin nuclear relocalization

ROSSO M,; BELGOROSKY D,; LAPYCKYJ L, ; LODILLINSKY C, ; EIJÁN AM,; VÁZQUEZ-LEVIN MH

San Juan

Congreso; SECOND JOINT MEETING OF THE BIOLOGY SOCIETIES FROM ARGENTINA; 2011

Sociedad Argentina de Biología

In bladder tumors, loss of epithelial cadherin (cadE), presence of neural (cadN) and placental (cadP) cadherin ("cadherin switch") and aberrant B-catenin localization is observed. B-catenin is phosphorylated in Ser 33 for degradation but, in abnormal conditions, it accumulates, translocates to the nucleus and activates genes related to invasion/metastasis. We have reported a decrease in cadE in a murine bladder cancer model, namely MB49/MB49I cells, being the latest more invasive. The aims of the research were: 1) To study the "cadherin switch", by evaluating expression of cadE, cadN and cadP and 2) To characterize expression of B-catenin. Studies were done in MB49I and MB49 cell cultures and orthotopic tumors using Western Immunoblotting, Immunocyto/histochemistry. 1) Low levels of mature cadE (120 kDa) were found in MB49 and no signal was detected in MB49I, 2) CadN was detected in both cell lines and cadP only in MB49I, 3) Total levels of B-catenin were higher in MB49I 4) B-catenin nuclear accumulation was found in MB49I cultures and tumors 5) A Ser33/fosfo-B-catenin lower signal was detected in MB49I compared to MB49 tumors. In conclusion, the study first describes changes in B-catenin phosphorylation during progression of bladder cancer using a murine experimental model.