ZNF50 3/ Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression

Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3169-3174. doi: 10.1073/pnas.1701690114. Epub 2017 Mar 3.

Abstract

The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for down-regulation of GATA3 via ZPO2. Through this modulation of GATA3 activity, ZPO2 promotes aggressive breast cancer development. Our data provide insight into a mechanism of GATA3 regulation, and identify ZPO2 as a possible candidate gene for future diagnostic and therapeutic strategies.

Keywords: GATA3; ZBTB32; ZNF503/ZPO2; breast cancer; tumor metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Binding Sites
  • Biopsy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Cluster Analysis
  • Disease Models, Animal
  • Disease Progression
  • Epithelial Cells / metabolism
  • Female
  • GATA3 Transcription Factor / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Heterografts
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Promoter Regions, Genetic
  • Protein Binding

Substances

  • GATA3 Transcription Factor