EXPRESSION OF DYSADHERIN AND RELATIONSHIP WITH TUMOR AGRESSIVENESS IN PROSTATE CANCER

MARINA ROSSO; MARÍA VICTORIA MENCUCCI; MONICA HEBE VAZQUEZ- LEVIN; BESSO M

Ciudad de Buenos Aires

Jornada; XVIII Jornadas Anuales Multidisciplinarias de la Sociedad Argentina de Biología.; 2016

Sociedad Argentina de BIología

Prostate cancer (PCa) is the 5th leading cause of cancer death among men worldwide. The loss of E-Cadherin (ECad) mediated cell-cell adhesion is a key event on PCa tumor progression and aggressiveness, but the underlying mechanisms are yet unknown. In previous studies we reported, for the first time, the expression of Dysadherin (Dys), a negative modulator of ECad expression/function(s), in PCa. Using established human PCa cell lines, Dys was found expressed at higher levels in more aggressive cell lines than in less aggressive ones. To further evaluate the relationship between Dys expression and PCa aggressiveness, two sets of studies were done: A) The human PCa PC3 cells were transiently transfected with a Dys-siRNA, and ECad expression and cell-cell adhesion was assessed. Moreover, PC3 cells were treated with TGF-β1 (a cytokine reported to promote a more aggressive phenotype in these cells) and Dys levels were evaluated. B) A PCa gene expression dataset (n=497 samples) from The Cancer Genome Atlas (TCGA) was analyzed to determine Dys expression levels and their association with ECad and TGF-β1 expression and with clinical parameters related to tumor aggressiveness (tumor stage, Gleason score, recurrence-free survival (RFS)). A) Dys-siRNA transfected PC3 cells showed negligible Dys expression compared to control cells and depicted increased (p