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Open AccessArticle

Tamoxifen Treatment of Breast Cancer Cells: Impact on Hedgehog/GLI1 Signaling

Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden
Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá 11001000, Colombia
Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia
Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy
Institute for Cancer Research and Treatment (IRCC), Strada Provinciale 142, 10060 Candiolo, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2016, 17(3), 308;
Received: 31 December 2015 / Revised: 17 February 2016 / Accepted: 22 February 2016 / Published: 27 February 2016
(This article belongs to the Collection Advances in Molecular Oncology)
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. View Full-Text
Keywords: GLI1; TAM resistance; breast cancer; Hedgehog signaling; cellular proliferation GLI1; TAM resistance; breast cancer; Hedgehog signaling; cellular proliferation
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Villegas, V.E.; Rondón-Lagos, M.; Annaratone, L.; Castellano, I.; Grismaldo, A.; Sapino, A.; Zaphiropoulos, P.G. Tamoxifen Treatment of Breast Cancer Cells: Impact on Hedgehog/GLI1 Signaling. Int. J. Mol. Sci. 2016, 17, 308.

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