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.

Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells / Barbetti V; Morandi A; Tusa I; Digiacomo G; Riverso M; Marzi I; Cipolleschi MG; Bessi S; Giannini A; Di Leo A; Dello Sbarba P; Rovida E.. - In: ONCOGENE. - ISSN 0950-9232. - STAMPA. - (2014), pp. 1-6. [10.1038/onc.2013.542]

Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells.

BARBETTI, VALENTINA;MORANDI, ANDREA;TUSA, IGNAZIA;DIGIACOMO, GRAZIANA;MARZI, ILARIA;CIPOLLESCHI, MARIA GRAZIA;DELLO SBARBA, PERSIO;ROVIDA, ELISABETTA
2014

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.
2014
1
6
Barbetti V; Morandi A; Tusa I; Digiacomo G; Riverso M; Marzi I; Cipolleschi MG; Bessi S; Giannini A; Di Leo A; Dello Sbarba P; Rovida E.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/832711
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