Tamoxifen treatment of breast cancer cells : Impact on Hedgehog/GLI1 signaling

The selective estrogen receptor (ER) modulator tamoxifen (TAM) has become the standard therapy for the treatment of ER+ breast cancer patients. Despite the obvious benefits of TAM, a proportion of patients acquire resistance to treatment, and this is a significant clinical problem. Consequently, the identification of possible mechanisms involved in TAM-resistance should help the development of new therapeutic targets. In this study, we present in vitro data using a panel of different breast cancer cell lines and demonstrate the modulatory effect of TAM on cellular proliferation and expression of Hedgehog signaling components, including the terminal effector of the pathway, the transcription factor GLI1. A variable pattern of expression following TAM administration was observed, reflecting the distinctive properties of the ER+ and ER´ cell lines analyzed. Remarkably, the TAM-induced increase in the proliferation of the ER+ ZR-75-1 and BT474 cells parallels a sustained upregulation of GLI1 expression and its translocation to the nucleus. These findings, implicating a TAM-GLI1 signaling cross-talk, could ultimately be exploited not only as a means for novel prognostication markers but also in efforts to effectively target breast cancer subtypes. © 2016 by the authors; licensee MDPI, Basel, Switzerland.

• Fecha de publicación: 2016
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/21353
• Acceso en línea: https://doi.org/10.3390/ijms17030308; https://repository.urosario.edu.co/handle/10336/21353
• Palabra clave: Hormona antineoplásica; Proteína GLI1; Tamoxifeno factor de transcripcion; Factor de transcripción Gli1; Cancer de mama; Enfermedades; Sonic hedgehog protein; Transcription factor Gli1; Antineoplastic hormone agonists and antagonists; Sonic hedgehog protein; Transcription factor; Transcription factor Gli1; human; GLI1 protein; Neoplasias; Tamoxifeno
• License: Abierto (Texto Completo)