Growth hormone-releasing hormone induced transactivation of epidermal growth factor receptor in human triple-negative breast cancer cells
Authors
Vacas Oliva, Eva; Muñoz Moreno, Laura; Valenzuela Ruiz, Pedro Luis; Prieto Villapún, Juan Carlos; Schally, Andrew V; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/59309DOI: 10.1016/j.peptides.2016.11.004
ISSN: 0196-9781
Date
2016-12Affiliation
Universidad de Alcalá. Departamento de Cirugía, Ciencias Médicas y Sociales; Universidad de Alcalá. Departamento de Biología de SistemasFunders
Hospital Universitario Príncipe de Asturias
Universidad de Alcalá
Bibliographic citation
Peptides, 2016, v. 86, p. 153-161
Keywords
GHRH
Triple-negative breast cancer
EGFR Transactivation
Cell migration
GHRH antagonist
Project
info:eu-repo/grantAgreement/HUPA//FIB-PI13-04/ES/
info:eu-repo/grantAgreement/UAH//CCG2014%2FBIO-028/ES/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/aceptedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Triple-negative breast cancer (TNBC) is a subset of breast cancers which is negative for expression of estrogen and progesterone receptors and human epidermal growth factor receptor-2 (HER2). Chemotherapy is currently the only form of treatment for women with TNBC. Growth hormone-releasing hormone (GHRH) and epidermal growth factor (EGF) are autocrine/paracrine growth factors in breast cancer and a substantial proportion of TNBC expresses receptors for GHRH and EGF. The aim of this study was to evaluate the interrelationship between both these signaling pathways in MDA-MB-468 human TNBC cells. We evaluated by Western blot assays the effect of GHRH on transactivation of EGF receptor (EGFR) as well as the elements implicated. We assessed the effect of GHRH on migration capability of MDA-MB-468 cells as well as the involvement of EGFR in this process by means of wound-healing assays. Our findings demonstrate that in MDA-MB-468 cells the stimulatory activity of GHRH on tyrosine phosphorylation of EGFR is exerted by two different molecular mechanisms: i) through GHRH receptors, GHRH stimulates a ligand-independent activation of EGFR involving at least cAMP/PKA and Src family signaling pathways; ii) GHRH also stimulates a ligand-dependent activation of EGFR implicating an extracellular pathway with an important role for metalloproteinases. The cross-talk between EGFR and GHRHR may be impeded by combining drugs acting upon GHRH receptors and EGFR family members. This combination of GHRH receptors antagonists with inhibitors of EGFR signalling could enhance the efficacy of both types of agents as well as reduce their doses increasing therapeutic benefits in management of human breast cancer.
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