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

Victoria E. Villegas, Milena Rondón-Lagos, Laura Annaratone, Isabella Castellano, Adriana Grismaldo, Anna Sapino, Peter G. Zaphiropoulos

Resultado de la investigación: Contribución a RevistaArtículo

10 Citas (Scopus)

Resumen

© 2016 by the authors; licensee MDPI, Basel, Switzerland.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.
Idioma originalEnglish (US)
PublicaciónInternational Journal of Molecular Sciences
DOI
EstadoPublished - feb 27 2016

Huella dactilar

estrogens
Tamoxifen
breast
cancer
Cells
Breast Neoplasms
Estrogen Receptors
cultured cells
effectors
Therapeutics
Transcription factors
Switzerland
markers
Selective Estrogen Receptor Modulators
Modulators
Cell Line
modulators
therapy
proportion
Estrogens

Citar esto

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. https://doi.org/10.3390/ijms17030308
Villegas, Victoria E. ; Rondón-Lagos, Milena ; Annaratone, Laura ; Castellano, Isabella ; Grismaldo, Adriana ; Sapino, Anna ; Zaphiropoulos, Peter G. / Tamoxifen treatment of breast cancer cells: Impact on Hedgehog/GLI1 signaling. En: International Journal of Molecular Sciences. 2016.
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abstract = "{\circledC} 2016 by the authors; licensee MDPI, Basel, Switzerland.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.",
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Tamoxifen treatment of breast cancer cells: Impact on Hedgehog/GLI1 signaling. / Villegas, Victoria E.; Rondón-Lagos, Milena; Annaratone, Laura; Castellano, Isabella; Grismaldo, Adriana; Sapino, Anna; Zaphiropoulos, Peter G.

En: International Journal of Molecular Sciences, 27.02.2016.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Tamoxifen treatment of breast cancer cells: Impact on Hedgehog/GLI1 signaling

AU - Villegas, Victoria E.

AU - Rondón-Lagos, Milena

AU - Annaratone, Laura

AU - Castellano, Isabella

AU - Grismaldo, Adriana

AU - Sapino, Anna

AU - Zaphiropoulos, Peter G.

PY - 2016/2/27

Y1 - 2016/2/27

N2 - © 2016 by the authors; licensee MDPI, Basel, Switzerland.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.

AB - © 2016 by the authors; licensee MDPI, Basel, Switzerland.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.

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