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题目:: Chromatin-associated CSF-1R binds to the promoter of proliferation-related genes in breast cancer cells.
作者:: Barbetti(V),Morandi(A),Tusa(I),Digiacomo(G),Riverso(M),Marzi(I),Cipolleschi(M G),Bessi(S),Giannini(A),Di Leo(A),Dello Sbarba(P),Rovida(E)
状态:: 发布时间2014-08-21 , 更新时间 2015-04-22
期刊:: Oncogene
摘要:: 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.
语言:: eng
DOI:

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