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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number308
JournalInternational Journal of Molecular Sciences
Issue number3
Publication statusPublished - Feb 27 2016


  • Breast cancer
  • Cellular proliferation
  • GLI1
  • Hedgehog signaling
  • TAM resistance

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications


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