title: ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium.
abstract: The telomeric amplicon at 8p12 is common in oestrogen receptor-positive (ER+) breast cancers. Array-CGH and expression analyses of 1172 primary breast tumours revealed that ZNF703 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor clinical outcome. ZNF703 transformed NIH 3T3 fibroblasts, behaving as a classical oncogene, and regulated proliferation in human luminal breast cancer cell lines and immortalized human mammary epithelial cells. Manipulation of ZNF703 expression in the luminal MCF7 cell line modified the effects of TGFβ on proliferation. Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.
authors.affiliation: Cancer Research UK, Cambridge Research Institute, Cambridge, UK.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Holland
authors.forename: Angela
authors.initials: A
authors.lastname: Burleigh
authors.forename: Anna
authors.initials: A
authors.lastname: Git
authors.forename: Mae A
authors.initials: MA
authors.lastname: Goldgraben
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Perez-Mancera
authors.forename: Suet-Feung
authors.initials: SF
authors.lastname: Chin
authors.forename: Antonio
authors.initials: A
authors.lastname: Hurtado
authors.forename: Alejandra
authors.initials: A
authors.lastname: Bruna
authors.forename: H Raza
authors.initials: HR
authors.lastname: Ali
authors.forename: Wendy
authors.initials: W
authors.lastname: Greenwood
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dunning
authors.forename: Shamith
authors.initials: S
authors.lastname: Samarajiwa
authors.forename: Suraj
authors.initials: S
authors.lastname: Menon
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Rueda
authors.forename: Andy G
authors.initials: AG
authors.lastname: Lynch
authors.forename: Steven
authors.initials: S
authors.lastname: McKinney
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
authors.forename: Jason S
authors.initials: JS
authors.lastname: Carroll
authors.forename: Christina
authors.initials: C
authors.lastname: Curtis
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells; D005260:Female; D005347:Fibroblasts; D020869:Gene Expression Profiling; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D015513:Oncogene Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D015513:Oncogene Proteins; C541016:ZNF703 protein, human