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   ELF5 Suppresses Estrogen Sensitivity and Underpins the Acquisition of Antiestrogen Resistance in Luminal Breast Cancer  
   
نویسنده kalyuga m. ,gallego-ortega d. ,lee h.j. ,roden d.l. ,cowley m.j. ,caldon c.e. ,stone a. ,allerdice s.l. ,valdes-mora f. ,launchbury r. ,statham a.l. ,armstrong n. ,alles m.c. ,young a. ,egger a. ,au w. ,piggin c.l. ,evans c.j. ,ledger a. ,brummer t. ,oakes s.r. ,kaplan w. ,gee j.m.w. ,nicholson r.i. ,sutherland r.l. ,swarbrick a. ,naylor m.j. ,clark s.j. ,carroll j.s. ,ormandy c.j.
منبع plos biology - 2012 - دوره : 10 - شماره : 12
چکیده    We have previously shown that during pregnancy the e-twenty-six (ets) transcription factor elf5 directs the differentiation of mammary progenitor cells toward the estrogen receptor (er)-negative and milk producing cell lineage,raising the possibility that elf5 may suppress the estrogen sensitivity of breast cancers. to test this we constructed inducible models of elf5 expression in er positive luminal breast cancer cells and interrogated them using transcript profiling and chromatin immunoprecipitation of dna followed by dna sequencing (chip-seq). elf5 suppressed er and foxa1 expression and broadly suppressed er-driven patterns of gene expression including sets of genes distinguishing the luminal molecular subtype. direct transcriptional targets of elf5,which included foxa1,egfr,and myc,accurately classified a large cohort of breast cancers into their intrinsic molecular subtypes,predicted er status with high precision,and defined groups with differential prognosis. knockdown of elf5 in basal breast cancer cell lines suppressed basal patterns of gene expression and produced a shift in molecular subtype toward the claudin-low and normal-like groups. luminal breast cancer cells that acquired resistance to the antiestrogen tamoxifen showed greatly elevated levels of elf5 and its transcriptional signature,and became dependent on elf5 for proliferation,compared to the parental cells. thus elf5 provides a key transcriptional determinant of breast cancer molecular subtype by suppression of estrogen sensitivity in luminal breast cancer cells and promotion of basal characteristics in basal breast cancer cells,an action that may be utilised to acquire antiestrogen resistance. © 2012 kalyuga et al.
آدرس cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,peter wills bioinformatics centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research uk,cambridge research institute,cambridge, United Kingdom, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,school of mathematics and statistics,prince of wales clinical school,university of new south wales kensington nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,university of bath,bath, United Kingdom, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,institute for molecular medicine and cell research,freiburg, Germany, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw, Australia, peter wills bioinformatics centre,garvan institute of medical research,darlinghurst,nsw,australia,st vincent's clinical school,st vincent's hospital and university of new south wales,darlinghurst nsw, Australia, breast cancer (molecular pharmacology) group,cardiff school of pharmacy and pharmaceutical science,cardiff university,cardiff,wales, United Kingdom, breast cancer (molecular pharmacology) group,cardiff school of pharmacy and pharmaceutical science,cardiff university,cardiff,wales, United Kingdom, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,st vincent's clinical school,st vincent's hospital and university of new south wales,darlinghurst nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,st vincent's clinical school,st vincent's hospital and university of new south wales,darlinghurst nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,st vincent's clinical school,st vincent's hospital and university of new south wales,darlinghurst nsw,australia,discipline of physiology and bosch institute,school of medical sciences,university of sydney,nsw, Australia, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,st vincent's clinical school,st vincent's hospital and university of new south wales,darlinghurst nsw, Australia, cancer research uk,cambridge research institute,cambridge, United Kingdom, cancer research program and the kinghorn cancer centre,garvan institute of medical research,darlinghurst,nsw,australia,st vincent's clinical school,st vincent's hospital and university of new south wales,darlinghurst nsw, Australia
 
     
   
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