title: Tamoxifen Treatment of Breast Cancer Cells: Impact on Hedgehog/GLI1 Signaling.
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.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden. victoria.villegas@urosario.edu.co.|Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá 11001000, Colombia. victoria.villegas@urosario.edu.co.|Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia. victoria.villegas@urosario.edu.co.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Villegas
authors.affiliation: Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia. srondonl@unito.it.|Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy. srondonl@unito.it.
authors.forename: Milena
authors.initials: M
authors.lastname: Rondón-Lagos
authors.affiliation: Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy. laura.annaratone@unito.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Annaratone
authors.affiliation: Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy. isabella.castellano@unito.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Castellano
authors.affiliation: Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 11001000, Colombia. mabel.grismaldo@urosario.edu.co.
authors.forename: Adriana
authors.initials: A
authors.lastname: Grismaldo
authors.affiliation: Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy. anna.sapino@unito.it.|Institute for Cancer Research and Treatment (IRCC), Strada Provinciale 142, 10060 Candiolo, Italy. anna.sapino@unito.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden. peter.zaphiropoulos@ki.se.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Zaphiropoulos
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D018931:Antineoplastic Agents, Hormonal; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D013629:Tamoxifen
keywords: GLI1; Hedgehog signaling; TAM resistance; breast cancer; cellular proliferation