title: Shift in GATA3 functions, and GATA3 mutations, control progression and clinical presentation in breast cancer.
abstract: BACKGROUND
  GATA binding protein 3 (GATA3) is a regulator of mammary luminal cell differentiation, and an estrogen receptor (ER) associated marker in breast cancer. Tumor suppressor functions of GATA3 have been demonstrated primarily in basal-like breast cancers. Here, we focused on its function in luminal breast cancer, where GATA3 is frequently mutated, and its levels are significantly elevated.
  
  
  METHODS
  GATA3 target genes were identified in normal- and luminal cancer- mammary cells by ChIP-seq, followed by examination of the effects of GATA3 expressions and mutations on tumorigenesis-associated genes and processes. Additionally, mutations and expression data of luminal breast cancer patients from The Cancer Genome Atlas were analyzed to characterize genetic signatures associated with GATA3 mutations.
  
  
  RESULTS
  We show that some GATA3 effects shift from tumor suppressing to tumor promoting during tumorigenesis, with deregulation of three genes, BCL2, DACH1, THSD4, representing major GATA3-controlled processes in cancer progression. In addition, we identify an altered activity of mutant GATA3, and distinct associated genetic signatures. These signatures depend on the functional domain mutated; and, for a specific subgroup, are shared with basal-like breast cancer patients, who are a clinical group with regard to considerations of mode of treatment.
  
  
  CONCLUSIONS
  The GATA3 dependent mechanisms may call for special considerations for proper prognosis and treatment of patients.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, 52900, Israel. helit.c@gmail.com.
authors.forename: Helit
authors.initials: H
authors.lastname: Cohen
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, 52900, Israel. rotem@systemsbiomed.org.
authors.forename: Rotem
authors.initials: R
authors.lastname: Ben-Hamo
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, 52900, Israel. moriahcohen@gmail.com.
authors.forename: Moriah
authors.initials: M
authors.lastname: Gidoni
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, 52900, Israel. ilana.brt@gmail.com.
authors.forename: Ilana
authors.initials: I
authors.lastname: Yitzhaki
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, 52900, Israel. renko1989@gmail.com.
authors.forename: Renana
authors.initials: R
authors.lastname: Kozol
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, 52900, Israel. alona.zilberberg@gmail.com.
authors.forename: Alona
authors.initials: A
authors.lastname: Zilberberg
authors.affiliation: The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan, 52900, Israel. sol.efroni@biu.ac.il.
authors.forename: Sol
authors.initials: S
authors.lastname: Efroni
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism*; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C000595707:BCL2 protein, human; C486747:DACH1 protein, human; D005136:Eye Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D019699:Thrombospondins; D014157:Transcription Factors; D051722:ADAM Proteins; C000602522:THSD4 protein, human