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BioMed Research International
Volume 2015, Article ID 761501, 12 pages
http://dx.doi.org/10.1155/2015/761501
Research Article

Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation

1Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio, s/n, Colegio Santo Tomas, 11340 México, DF, Mexico
2Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias (UIMEIP), Hospital de Pediatría, CMN Siglo-XXI, Instituto Mexicano del Seguro Social (IMSS), Avenida Cuauhtémoc No. 330, Colegio Doctores, 06720 México, DF, Mexico
3Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Colegio Doctores, 06720 México, DF, Mexico
4Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional No. 2508, Colegio San Pedro Zacatenco, 07360 México, DF, Mexico
5Facultad de Química, Universidad Nacional Autónoma de México, Avenida Universidad No. 3000, Colegio Universidad Nacional Autónoma, 04510 México, DF, Mexico
6Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, CMN Siglo-XXI, Instituto Mexicano del Seguro Social (IMSS), Avenida Cuauhtémoc No. 330, Colegio Doctores, 06720 México, DF, Mexico

Received 4 March 2015; Revised 16 April 2015; Accepted 20 April 2015

Academic Editor: Sandra Marmiroli

Copyright © 2015 Gabriela Vallejo-Flores et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion.