Open AccessZNF50 3/ Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression
Author(s) -
Payam Shahi,
ChihYang Wang,
Devon A. Lawson,
Euan M. Slorach,
Angela Lu,
Ying Yu,
Ming-Derg Lai,
Hugo González Velozo,
Zena Werb
Publication year - 2017
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1701690114
Subject(s) - gata3 , breast cancer , estrogen receptor , zinc finger , transcription factor , cancer research , phenotype , ectopic expression , estrogen receptor alpha , medicine , repressor , biology , estrogen , cancer , oncology , gene , genetics
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.
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