title: Role of 3'-5'-cyclic adenosine monophosphate on the epidermal growth factor dependent survival in mammary epithelial cells.
abstract: Epidermal growth factor (EGF) has been suggested to play a key role in the maintenance of epithelial cell survival during lactation. Previously, we demonstrated that EGF dependent activation of PI3K pathway prevents apoptosis in confluent murine HC11 cells cultured under low nutrient conditions. The EGF protective effect is associated with increased levels of the antiapoptotic protein Bcl-XL. Here, we identify the EGF-dependent mechanism involved in cell survival that converges in the regulation of bcl-X expression 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 and the 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 and the adenylate cyclase that would have an impact in preventing apoptosis under low nutrient conditions.
authors.affiliation: Departamento de Química Biológica, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina; IFIBYNE (UBA-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Diego Y
authors.initials: DY
authors.lastname: Grinman
authors.affiliation: LIAN-CONICET, Fundación para la Lucha contra las Enfermedades Neurodegenerativas de la Infancia, Ruta 9, Km. 52,5, Escobar, B1625XAF, Provincia de Buenos Aires, Argentina.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Romorini
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, NIH, Building 41, B602, 41 Library Drive, Bethesda, MD, 20892, USA.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Presman
authors.affiliation: Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina; IFIBYNE (UBA-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Rocha-Viegas
authors.affiliation: Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina; IFIBYNE (UBA-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Coso
authors.affiliation: Cátedra de Química Medicinal, Departamento de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina; Instituto de Investigaciones Farmacológicas, ININFA-UBA-CONICET, Junin 954, C1113AAD, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Davio
authors.affiliation: Departamento de Química Biológica, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina; IFIBYNE (UBA-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: apecci@qb.fcen.uba.ar.
authors.forename: Adali
authors.initials: A
authors.lastname: Pecci
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000187:drug effects; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494812:Bcl2l1 protein, mouse; C492004:Creb1 protein, mouse; D003470:Culture Media; D017362:Cyclic AMP Response Element-Binding Protein; D051020:bcl-X Protein; D004815:Epidermal Growth Factor; D000242:Cyclic AMP
keywords: Apoptosis; CREB; EGF; Mammary epithelial cells; bcl-X; cAMP