title: HuR is necessary for mammary epithelial cell proliferation and polarity at least in part via ΔNp63.
abstract: HuR, a RNA binding protein, is known to function as a tumor maintenance gene in breast cancer and associated with tumor growth and poor prognosis. However, the cellular function of this protein remains largely unknown in normal mammary epithelial cells. Here, we showed that in immortalized MCF10A mammary epithelial cells, HuR knockdown inhibits cell proliferation and enhances premature senescence. We also showed that in three-dimensional culture, MCF10A cells with HuR knockdown form abnormal acini with filled lumen and an aberrant expression pattern of the extracellular matrix protein laminin V. In addition, we showed that HuR knockdown increases ΔNp63, but decreases wild-type p53, expression in MCF10A cells. Moreover, we showed that ΔNp63 knockdown partially rescues the proliferative defect induced by HuR knockdown in MCF10A cells. Consistent with this, we identified two U-rich elements in the 3'-untranslated region of p63 mRNA, to which HuR specifically binds. Finally, we showed that HuR knockdown enhances ΔNp63 mRNA translation but has no effect on p63 mRNA turnover. Together, our data suggest that HuR maintains cell proliferation and polarity of mammary epithelial cells at least in part via ΔNp63.
authors.affiliation: Comparative Oncology Laboratory, University of California Davis, Davis, California, United States of America.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yan
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Seong-Jun
authors.initials: SJ
authors.lastname: Cho
authors.forename: Xinbin
authors.initials: X
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology*; D049109:Cell Proliferation; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; C081876:CKAP4 protein, human; D051959:ELAV Proteins; D008565:Membrane Proteins