PI3K molecular pathway modulates p63 transcription factor protein levels in bladder cancer (BC)

ZAMBRANO, MACARENA;; SCIACCA, MARIANELA; ; BELGOROSKY, DENISE;; LANGLE, YANINA; ; SANDES, EDUARDO;; ANA MARIA EIJAN; LODILLINSKY, CATALINA.

Congreso; Reunion Anual de Sociedades de Biomediciencia; 2019

Based in the need to develop more precise therapies, bladder cancer has been classified related to its gene expression. The biological and clinical significance of these signatures remains unclear. p63 characterize two important groups: Luminal Papillary and Basal/Squamous bladder tumors (Kamoun, 2018). Our hypothesis is that p63 acts as a protumoral factor, by activation of invasive signaling programs. Our previous results showed that p63 depleted bladder cancer cells have lower extracellular matrix degradation, migratory capacity, 3D and in-vivo growth rate than controls. In order to identify possible molecular pathways that modulate p63 and that could eventually be drug molecular targets, UMUC14 BC cells were treated with inhibitors of different pathways SB20358 (p38 pathway), PD98059 (MAPK pathway), LY29002 (PI3K pathway). p63 expression was tested by western blot. 2D growth was measured by MTS. UMUC14 cells were grown in 3D conditions during 30 days treated with or without inhibitors and spheroids diameter was measured.All of the inhibitors showed a decrease in p63 expression, being LY29002 the one that showed the best and most sustained effect over time. This decrease in p63 expression (52% less expression p