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ELF5 Drives Lung Metastasis in Luminal Breast Cancer through Recruitment of Gr1+ CD11b+ Myeloid-Derived Suppressor Cells
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نویسنده
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gallego-ortega d. ,ledger a. ,roden d.l. ,law a.m.k. ,magenau a. ,kikhtyak z. ,cho c. ,allerdice s.l. ,lee h.j. ,valdes-mora f. ,herrmann d. ,salomon r. ,young a.i.j. ,lee b.y. ,sergio c.m. ,kaplan w. ,piggin c. ,conway j.r.w. ,rabinovich b. ,millar e.k.a. ,oakes s.r. ,chtanova t. ,swarbrick a. ,naylor m.j. ,o’toole s. ,green a.r. ,timpson p. ,gee j.m.w. ,ellis i.o. ,clark s.j. ,ormandy c.j.
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منبع
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plos biology - 2015 - دوره : 13 - شماره : 12
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چکیده
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During pregnancy,the ets transcription factor elf5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. in breast cancer,elf5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. in the mouse mammary tumor virus-polyoma middle t (mmtv-pymt) model of luminal breast cancer,induction of elf5 levels increased leukocyte infiltration,angiogenesis,and blood vessel permeability in primary tumors and greatly increased the size and number of lung metastasis. myeloid-derived suppressor cells,a group of immature neutrophils recently identified as mediators of vasculogenesis and metastasis,were recruited to the tumor in response to elf5. depletion of these cells using specific ly6g antibodies prevented elf5 from driving vasculogenesis and metastasis. expression signatures in luminal a breast cancers indicated that increased myeloid cell invasion and inflammation were correlated with elf5 expression,and increased elf5 immunohistochemical staining predicted much shorter metastasis–free and overall survival of luminal a patients,defining a group who experienced unexpectedly early disease progression. thus,in the mmtv-pymt mouse mammary model,increased elf5 levels drive metastasis by co-opting the innate immune system. as elf5 has been previously implicated in the development of antiestrogen resistance,this finding implicates elf5 as a defining factor in the acquisition of the key aspects of the lethal phenotype in luminal a breast cancer. © 2015 gallego-ortega et al.
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آدرس
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garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,epigenetics isp,babraham institute,cambridge, United Kingdom, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, peter wills bioinformatic center,garvan institute of medical research,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, the university of texas md anderson cancer center,houstontx, United States, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,department of anatomical pathology seals,st. george hospital,kogarah,nsw,australia,school of medicine and health sciences,university of western sydney,campbelltown,new south wales, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,sydney medical school,university of sydney,camperdown,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,sydney medical school,university of sydney,camperdown,nsw, Australia, department of histopathology,nottingham city hospital and nottingham university,nottingham, United Kingdom, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, cardiff school of pharmacy and pharmaceutical sciences,cardiff university,cardiff, United Kingdom, department of histopathology,nottingham city hospital and nottingham university,nottingham, United Kingdom, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia, garvan institute of medical research and the kinghorn cancer centre,darlinghurst,nsw,australia,st. vincent’s clinical school of medicine,university of new south wales,darlinghurst,nsw, Australia
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Authors
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