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

Shahi, Payam; Wang, Chih-Yang; Lawson, Devon A; Slorach, Euan M; Lu, Angela; Yu, Ying; Lai, Ming-Derg; Gonzalez Velozo, Hugo et al. · Proc Natl Acad Sci U S A · 2017

basic_science · Level V

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Abstract

The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of <i>GATA3</i> 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 <i>GATA3</i> expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to <i>GATA3</i> promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for down-regulation of <i>GATA3</i> 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.

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