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10.3390/ijms17030308
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Article

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

by
Victoria E. Villegas
1,2,3,*,†,
Milena Rondón-Lagos
3,4,†,
Laura Annaratone
4,
Isabella Castellano
4,
Adriana Grismaldo
3,
Anna Sapino
4,5 and
Peter G. Zaphiropoulos
1
1
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden
2
Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá 11001000, Colombia
3
Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia
4
Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy
5
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.
Int. J. Mol. Sci. 2016, 17(3), 308; https://doi.org/10.3390/ijms17030308
Submission received: 31 December 2015 / Revised: 17 February 2016 / Accepted: 22 February 2016 / Published: 27 February 2016
(This article belongs to the Special Issue Advances in Molecular Oncology)
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Abstract

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.
Keywords: GLI1; TAM resistance; breast cancer; Hedgehog signaling; cellular proliferation GLI1; TAM resistance; breast cancer; Hedgehog signaling; cellular proliferation
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MDPI and ACS Style

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. https://doi.org/10.3390/ijms17030308

AMA Style

Villegas VE, Rondón-Lagos M, Annaratone L, Castellano I, Grismaldo A, Sapino A, Zaphiropoulos PG. Tamoxifen Treatment of Breast Cancer Cells: Impact on Hedgehog/GLI1 Signaling. International Journal of Molecular Sciences. 2016; 17(3):308. https://doi.org/10.3390/ijms17030308

Chicago/Turabian Style

Villegas, Victoria E., Milena Rondón-Lagos, Laura Annaratone, Isabella Castellano, Adriana Grismaldo, Anna Sapino, and Peter G. Zaphiropoulos. 2016. "Tamoxifen Treatment of Breast Cancer Cells: Impact on Hedgehog/GLI1 Signaling" International Journal of Molecular Sciences 17, no. 3: 308. https://doi.org/10.3390/ijms17030308

APA Style

Villegas, V. E., Rondón-Lagos, M., Annaratone, L., Castellano, I., Grismaldo, A., Sapino, A., & Zaphiropoulos, P. G. (2016). Tamoxifen Treatment of Breast Cancer Cells: Impact on Hedgehog/GLI1 Signaling. International Journal of Molecular Sciences, 17(3), 308. https://doi.org/10.3390/ijms17030308

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