title: The Transcriptional Repressor ZNF503/Zeppo2 Promotes Mammary Epithelial Cell Proliferation and Enhances Cell Invasion.
abstract: The NET (nocA, Nlz, elB, TLP-1) subfamily of zinc finger proteins is an important mediator during developmental processes. The evolutionary conserved zinc finger protein ZNF503/Zeppo2 (zinc finger elbow-related proline domain protein 2, Zpo2) plays critical roles during embryogenesis. We found that Zpo2 is expressed in adult tissue and examined its function. We found that ZPO2 is a nuclearly targeted transcriptional repressor that is expressed in mammary epithelial cells. Elevated Zpo2 levels increase mammary epithelial cell proliferation. Zpo2 promotes cellular invasion through down-regulation of E-cadherin and regulates the invasive phenotype in a RAC1-dependent manner. We detect elevated Zpo2 expression during breast cancer progression in a MMTV-PyMT transgenic mouse model. Tumor transplant experiments indicated that overexpression of Zpo2 in MMTV-PyMT mammary tumor cell lines enhances lung metastasis. Our findings suggest that Zpo2 plays a significant role in mammary gland homeostasis and that deregulation of Zpo2 may promote breast cancer development.
authors.affiliation: From the Department of Anatomy, University of California, San Francisco, California 94143-0452 and.
authors.forename: Payam
authors.initials: P
authors.lastname: Shahi
authors.affiliation: From the Department of Anatomy, University of California, San Francisco, California 94143-0452 and.
authors.forename: Euan M
authors.initials: EM
authors.lastname: Slorach
authors.affiliation: the Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Wang
authors.affiliation: From the Department of Anatomy, University of California, San Francisco, California 94143-0452 and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chou
authors.affiliation: From the Department of Anatomy, University of California, San Francisco, California 94143-0452 and.
authors.forename: Angela
authors.initials: A
authors.lastname: Lu
authors.affiliation: From the Department of Anatomy, University of California, San Francisco, California 94143-0452 and.
authors.forename: Aline
authors.initials: A
authors.lastname: Ruderisch
authors.affiliation: From the Department of Anatomy, University of California, San Francisco, California 94143-0452 and zena.werb@ucsf.edu.
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D047908:Intracellular Signaling Peptides and Proteins; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C483194:Zfp503 protein, mouse; D020830:rac1 GTP-Binding Protein
keywords: Breast Cancer; Cancer Biology; Cell Migration; E-cadherin; Focal Adhesion Kinase (FAK); Grg4; Invasion; PTK2 Protein Tyrosine Kinase 2 (PTK2); Proliferation; Src; ZNF503