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

Daniel G. Holland, Angela Burleigh, Anna Git, Mae A. Goldgraben, Pedro A. Perez-Mancera, Suet Feung Chin, Antonio Hurtado, Alejandra Bruna, H. Raza Ali, Wendy Greenwood, Mark J. Dunning, Shamith Samarajiwa, Suraj Menon, Oscar M. Rueda, Andy G. Lynch, Steven McKinney, Ian O. Ellis, Connie J. Eaves, Jason S. Carroll, Christina CurtisSamuel Aparicio, Carlos Caldas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)167-180
Number of pages14
JournalEmbo Molecular Medicine
Volume3
Issue number3
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Breast cancer
  • Luminal B
  • Oestrogen metabolism
  • Oncogene
  • ZNF703

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