Specific role of AKT isoforms in PC3 proliferation and differentiation

ARIEL E. CARIAGA-MARTINEZ; JAVIER RODRIGUEZ-UBREVA; M. ALICIA CORTÉS; PILAR LÓPEZ-RUIZ; BEGOÑA COLÁS

Vienna

Congreso; 32nd FEBS Molecular Machines; 2007

FEBS

The Ser/Thr kinase Akt, the major downstream PI3K pathway effector, seems to be a versatile mediator in different cellular func- tions, including apoptosis and cell cycle regulation. Three Akt iso- forms, with different tissue expression patterns, have been identified. The importance of this signaling pathway for cell survi- val, in the absence of androgens, is obvious since treatment with the PI3K inhibitor LY-294002 leads to apoptosis in LNCaP cells and to inhibition of cell proliferation in PC3 cells. Our results show that the decrease of Akt2 expression by siRNA modified the normal PC3 spindle-shaped morphology, which became tightly packed and cuboidal in appearance, characteristic of normal epi- thelial cells. We also observed an increase of E-cadherin levels. Furthermore, the reduction of Akt2 levels significantly decreased PC3 cell proliferation. Under these conditions, we observed a strong activation of ERK1/2, an increase of p27and a decrease of both cycline D1and cycline E levels. The reduction of AKt1 lev- els, however, decreased the expression of E-cadherins, without altering cell morphology. Under these conditions, cell proliferationwas decreased, concomitantly with an increase of p27. No changes in cycline levels were observed. Our results suggest specific roles of each Akt isoform in cell proliferation and differentiation.