EGF-dependent bcl-X expression in mammary epithelial cells

GRINMAN, D; ROMORINI, L.; COSO, O.A.; PECCI, A.

Los Cocos, Cordoba

Workshop; SISTAM 2010; 2010

EGF activates signaling pathways asociated with celular proliferation and apoptosis. We have previously shown that the expression of the antiapoptotic protein Bcl-XL is regulated by EGF throughout apoptosis inhibition in HC11 mammary epithelial cells, being PI3K/AKT the main pathway involved in this process. EGF mediated bcl-X induction occurs mainly through the activation of bcl-X promoter P1, which contains CREB and ETS response elements. In this work we analyzed the possible participation of these transcription factors on EGF dependent bcl-X expression. HC11 cells where co-transfected with a pP1-Luc reporter vector together with pAKT and the above mentioned transcription factors expression vectors. Results showed that CREB induced bcl-X P1activation response (3,5±0,2 folds). Co-transfeccions of P1-Luc and a CREB dominant negative expression vector confirmed P1 as a CREB target. Moreover, EGF-dependent CREB phosphorylation was also observed. Conclusions: PI3K/AKT activation by EGF increases bcl-X levels by regulating P1, being CREB a potential transcription factor mediating this effect.