title: ZNF503/Zpo2drives aggressive breast cancer progression by down-regulation of GATA3 expression.
abstract: The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss ofGATA3is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor ofGATA3expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited toGATA3promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for down-regulation ofGATA3via 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.
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143.
authors.forename: Payam
authors.initials: P
authors.lastname: Shahi
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143.
authors.forename: Devon A
authors.initials: DA
authors.lastname: Lawson
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143.
authors.forename: Euan M
authors.initials: EM
authors.lastname: Slorach
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143.
authors.forename: Angela
authors.initials: A
authors.lastname: Lu
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Ming-Derg
authors.initials: MD
authors.lastname: Lai
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gonzalez Velozo
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143; zena.werb@ucsf.edu.
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
mesh_terms: D000818:Animals; D001665:Binding Sites; D001706:Biopsy; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D011485:Protein Binding
chemical_list: D050990:GATA3 Transcription Factor
keywords: GATA3; ZBTB32; ZNF503/ZPO2; breast cancer; tumor metastasis