國家衛生研究院 NHRI:Item 3990099045/11270
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 856786      Online Users : 903
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version
    NHRI > NHRI Graduate Student Program > Others > Periodical Articles >  Item 3990099045/11270


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11270


    Title: Dehydroepiandrosterone induces temozolomide resistance through modulating phosphorylation and acetylation of Sp1 in glioblastoma
    Authors: Yang, WB;Chuang, JY;Ko, CY;Chang, WC;Hsu, TI
    Contributors: NHRI Graduate Student Program
    Abstract: Glioblastoma is the most malignant type of brain tumor for which there are currently no effective treatments. Patient prognosis is improved by radiation combined with temozolomide (TMZ) therapy but only for a short period of time due to the high prevalence of recurrence. Although O(6)-methylguanine-DNA methyltransferase (MGMT)-mediated DNA repair is a well-defined characteristic of TMZ resistance, the mechanism by which MGMT-deficient glioblastoma counteracts TMZ-induced DNA damage, leading to apoptosis, still remains unclear. Previously, we determined that aberrantly activated cytochrome P450 17A1 causes TMZ resistance in MGMT-deficient glioblastoma by increasing the secretion of dehydroepiandrosterone (DHEA), a neurosteroid that maintains the health of neurons and astrocytes. However, the precise mechanism by which DHEA alters the response of glioblastoma to TMZ has not been studied. In the present study, we found that DHEA prevents TMZ-induced apoptosis by attenuating DNA damage in MGMT-deficient glioblastoma. In addition, DHEA activated the LYN-AKT cascade to induce Sp1 phosphorylation. Phospho-Sp1 localized in TMZ-damaged DNA, prevented further DNA damage, and was deacetylated through the recruitment of HDAC1/2. Deacetylated Sp1 recruited proliferating cell nuclear antigen (PCNA) to attenuate DNA damage. To confirm whether the DHEA-induced cellular process contributes to TMZ resistance, we established a TMZ-resistant glioblastoma cell line, A172R, and isolated primary resistant tumor cells, PtR#1, from a glioblastoma patient exhibiting chemotherapeutic resistance. Sp1 exhibited phosphorylated and deacetylated status, and associated with HDAC1/2 and PCNA in TMZ-resistant cells. Based on these findings, we conclude that DHEA induces TMZ resistance in glioblastoma via the induction of phospho-Sp1-mediated DNA repair.
    Date: 2019-04
    Relation: Molecular Neurobiology. 2019 Apr;56(4):2301-2313.
    Link to: http://dx.doi.org/10.1007/s12035-018-1221-7
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0893-7648&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000465498200001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85050213966
    Appears in Collections:[Others] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    PUB30022431.pdf2398KbAdobe PDF250View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback