ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression

Payam Shahi, Chih Yang Wang, Devon A. Lawson, Euan M. Slorach, Angela Lu, Ying Yu, Ming Derg Lai, Hugo Gonzalez Velozo, Zena Werb

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 downregulation 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.

Original languageEnglish
Pages (from-to)3169-3174
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number12
DOIs
Publication statusPublished - 2017 Mar 21

All Science Journal Classification (ASJC) codes

  • General

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