title: Bioluminescence imaging of estrogen receptor activity during breast cancer progression.
abstract: Estrogen receptors (ER) are known to play an important regulatory role in mammary gland development as well as in its neoplastic transformation. Although several studies highlighted the contribution of ER signaling in the breast transformation, little is known about the dynamics of ER state of activity during carcinogenesis due to the lack of appropriate models for measuring the extent of receptor signaling in time, in the same animal. To this aim, we have developed a reporter mouse model for the non-invasive in vivo imaging of ER activity: the ERE-Luc reporter mouse. ERE-Luc is a transgenic mouse generated with a firefly luciferase (Luc) reporter gene driven by a minimal promoter containing an estrogen responsive element (ERE). This model allows to measure receptor signaling in longitudinal studies by bioluminescence imaging (BLI). Here, we have induced sporadic mammary cancers by treating systemically ERE-Luc reporter mice with DMBA (9,10-dimethyl 1,2-benzanthracene) and measured receptor signaling by in vivo imaging in individual animals from early stage until a clinically palpable tumor appeared in the mouse breast. We showed that DMBA administration induces an increase of bioluminescence in the whole abdominal area 6 h after treatment, the signal rapidly disappears. Several weeks later, strong bioluminescence is observed in the area corresponding to the mammary glands. In vivo and ex vivo imaging analysis demonstrated that this bioluminescent signal is localized in the breast area undergoing neoplastic transformation. We conclude that this non-invasive assay is a novel relevant tool to identify the activation of the ER signaling prior the morphological detection of the neoplastic transformation.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan 20133, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Vantaggiato
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan 20133, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Dell'Omo
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan 20133, Milan, Italy.
authors.forename: Balaji
authors.initials: B
authors.lastname: Ramachandran
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute Via Elio Chianesi 53, 00144, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Manni
authors.affiliation: Mouse & Animal Pathology Lab, Fondazione Filarete Viale Ortles 22/4 - 20139, Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Radaelli
authors.affiliation: Mouse & Animal Pathology Lab, Fondazione Filarete Viale Ortles 22/4 - 20139, Milano, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Scanziani
authors.affiliation: Department of Research, Advanced Diagnostics and Technological Innovation, Regina Elena National Cancer Institute Via Elio Chianesi 53, 00144, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Piaggio
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan 20133, Milan, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Maggi
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Center of Excellence on Neurodegenerative Diseases, University of Milan 20133, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciana
keywords: Mammary tumorigenesis; chemical carcinogenesis; hormone-dependent cancer; optical imaging