title: PDEF promotes luminal differentiation and acts as a survival factor for ER-positive breast cancer cells.
abstract: Breast cancer is a heterogeneous disease and can be classified based on gene expression profiles that reflect distinct epithelial subtypes. We identify prostate-derived ETS factor (PDEF) as a mediator of mammary luminal epithelial lineage-specific gene expression and as a factor required for tumorigenesis in a subset of breast cancers. PDEF levels strongly correlate with estrogen receptor (ER)-positive luminal breast cancer, and PDEF transcription is inversely regulated by ER and GATA3. Furthermore, PDEF is essential for luminal breast cancer cell survival and is required in models of endocrine resistance. These results offer insights into the function of this ETS factor that are clinically relevant and may be of therapeutic value for patients with breast cancer treated with endocrine therapy.
authors.affiliation: Division of Molecular and Cellular Oncology, Department of Medical Oncology, and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Gilles
authors.initials: G
authors.lastname: Buchwalter
authors.forename: Michele M
authors.initials: MM
authors.lastname: Hickey
authors.forename: Anne
authors.initials: A
authors.lastname: Cromer
authors.forename: Laura M
authors.initials: LM
authors.lastname: Selfors
authors.forename: Ruwanthi N
authors.initials: RN
authors.lastname: Gunawardane
authors.forename: Jason
authors.initials: J
authors.lastname: Frishman
authors.forename: Rinath
authors.initials: R
authors.lastname: Jeselsohn
authors.forename: Elgene
authors.initials: E
authors.lastname: Lim
authors.forename: David
authors.initials: D
authors.lastname: Chi
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Fu
authors.forename: Rachel
authors.initials: R
authors.lastname: Schiff
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.forename: Joan S
authors.initials: JS
authors.lastname: Brugge
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism / Q000502:physiology; D006801:Humans; D061986:MCF-7 Cells; D011379:Prognosis; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C491901:FAS protein, human; C496499:FOXA1 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D050783:Proto-Oncogene Proteins c-ets; D011960:Receptors, Estrogen; C403974:SPDEF protein, human; D019014:fas Receptor