Role of 3'-5'-cyclic adenosine monophosphate on the epidermal growth factor dependent survival in mammary epithelial cells

DIEGO Y. GRINMAN; LEONARDO ROMORINI; DIEGO M. PRESMAN; LUCIANA ROCHA VIEGAS; OMAR A. COSO; DAVIO CARLOS; PECCI ADALI

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2016 vol. 419 p. 259 - 267

0303-7207

Epidermal growth factor (EGF) has been suggested to play a key role in the maintenance of epithelial cellsurvival during lactation. Previously, we demonstrated that EGF dependent activation of PI3K pathwayprevents apoptosis in confluent murine HC11 cells cultured under low nutrient conditions. The EGFprotective effect is associated with increased levels of the antiapoptotic protein Bcl-XL. Here, we identifythe EGF-dependent mechanism involved in cell survival that converges in the regulation of bcl-Xexpression by activated CREB. EGF induces Bcl-XL expression through activation of a unique bcl-X promoter,the P1; being not only the PI3K/AKT signaling pathway but also the increase in cAMP levels andthe concomitant PKA/CREB activation necessary for both bcl-XL upregulation and apoptosis avoidance.Results presented in this work suggest the existence of a novel connection between the EGF receptor andthe adenylate cyclase that would have an impact in preventing apoptosis under low nutrient conditions.