title: Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells.
abstract: The colony-stimulating factor-1 (CSF-1) and its receptor CSF-1R physiologically regulate the monocyte/macrophage system, trophoblast implantation and breast development. An abnormal CSF-1R expression has been documented in several human epithelial tumors, including breast carcinomas. We recently demonstrated that CSF-1/CSF-1R signaling drives proliferation of breast cancer cells via 'classical' receptor tyrosine kinase signaling, including activation of the extracellular signal-regulated kinase 1/2. In this paper, we show that CSF-1R can also localize within the nucleus of breast cancer cells, either cell lines or tissue specimens, irrespectively of their intrinsic molecular subtype. We found that the majority of nuclear CSF-1R is located in the chromatin-bound subcellular compartment. Chromatin immunoprecipitation revealed that CSF-1R, once in the nucleus, binds to the promoters of the proliferation-related genes CCND1, c-JUN and c-MYC. CSF-1R also binds the promoter of its ligand CSF-1 and positively regulates CSF-1 expression. The existence of such a receptor/ligand regulatory loop is a novel aspect of CSF-1R signaling. Moreover, our results provided the first evidence of a novel localization site of CSF-1R in breast cancer cells, suggesting that CSF-1R could act as a transcriptional regulator on proliferation-related genes.
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Barbetti
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Morandi
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Tusa
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Digiacomo
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Riverso
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Marzi
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Cipolleschi
authors.affiliation: Anatomia Patologica, Ospedale di Prato, Prato, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bessi
authors.affiliation: Anatomia Patologica, Ospedale di Prato, Prato, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giannini
authors.affiliation: 8216;Sandro Pitigliani' Medical Oncology Unit, Department of Oncology, Hospital of Prato, IstitutoToscanoTumori, Prato, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Dello Sbarba
authors.affiliation: Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Sezione di Patologia, Universitá degli Studi di Firenze, Istituto Toscano Tumori, Firenze, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Rovida
mesh_terms: D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism*; D025461:Feedback, Physiological; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021381:Protein Transport; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015398:Signal Transduction; D012995:Solubility; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D016186:Receptor, Macrophage Colony-Stimulating Factor