• Login
    View Item 
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    •   Home
    • UMass Chan Faculty and Staff Research and Publications
    • UMass Chan Faculty and Researcher Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of eScholarship@UMassChanCommunitiesPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywordsThis CollectionPublication DateAuthorsUMass Chan AffiliationsTitlesDocument TypesKeywords

    My Account

    LoginRegister

    Help

    AboutSubmission GuidelinesData Deposit PolicySearchingAccessibilityTerms of UseWebsite Migration FAQ

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Estrogen receptor beta sustains epithelial differentiation by regulating prolyl hydroxylase 2 transcription

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Mak, Paul
    Chang, Cheng
    Pursell, Bryan M.
    Mercurio, Arthur M.
    UMass Chan Affiliations
    Department of Cancer Biology
    Document Type
    Journal Article
    Publication Date
    2013-03-19
    Keywords
    Cell Differentiation
    Cell Line, Tumor
    Epithelial Cells
    Estrogen Receptor beta
    Gene Expression Regulation, Enzymologic
    Humans
    Hydroxylation
    Hypoxia-Inducible Factor 1, alpha Subunit
    Male
    Mutation
    Procollagen-Proline Dioxygenase
    Protein Stability
    Proteolysis
    Response Elements
    Transcription, Genetic
    Cancer Biology
    Show allShow less
    
    Metadata
    Show full item record
    Link to Full Text
    http://dx.doi.org/10.1073/pnas.1221654110
    Abstract
    Estrogen receptor beta (ERbeta) promotes the degradation of hypoxia inducible factor 1alpha (HIF-1alpha), which contributes to the ability of this hormone receptor to sustain the differentiation of epithelial and carcinoma cells. Although the loss of ERbeta and consequent HIF-1 activation occur in prostate cancer with profound consequences, the mechanism by which ERbeta promotes the degradation of HIF-1alpha is unknown. We report that ERbeta regulates the ligand (3beta-adiol)-dependent transcription of prolyl hydroxylase 2 (PHD2) also known as Egl nine homolog 1 (EGLN1), a 2-oxoglutarate-dependent dioxygenase that hydroxylates HIF-1alpha and targets it for recognition by the von Hippel-Lindau tumor suppressor and consequent degradation. ERbeta promotes PHD2 transcription by interacting with a unique estrogen response element in the 5' UTR of the PHD2 gene that functions as an enhancer. PHD2 itself is critical for maintaining epithelial differentiation. Loss of PHD2 expression or inhibition of its function results in dedifferentiation with characteristics of an epithelial-mesenchymal transition, and exogenous PHD2 expression in dedifferentiated cells can restore an epithelial phenotype. Moreover, expression of HIF-1alpha in cells that express PHD2 does not induce dedifferentiation but expression of HIF-1alpha containing mutations in the proline residues that are hydroxylated by PHD2 induces dedifferentiation. These data describe a unique mechanism for the regulation of HIF-1alpha stability that involves ERbeta-mediated transcriptional regulation of PHD2 and they highlight an unexpected role for PHD2 in maintaining epithelial differentiation.
    Source
    Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4708-13. doi: 10.1073/pnas.1221654110. Link to article on publisher's site
    DOI
    10.1073/pnas.1221654110
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/29142
    PubMed ID
    23487784
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.1221654110
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications

    entitlement

    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Lamar Soutter Library, UMass Chan Medical School | 55 Lake Avenue North | Worcester, MA 01655 USA
    Quick Guide | escholarship@umassmed.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.