<i>ZNF703</i> is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium

Abstract

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.

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Affiliated Institutions

• University of British Columbia CA
• University of Southern California US
• Nottingham University Hospitals NHS Trust GB
• University of Cambridge GB
• BC Cancer Agency CA
• Cancer Research UK Cambridge Center GB

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