Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Medicine / 醫學院
  3. Clinical Laboratory Sciences and Medical Biotechnology / 醫學檢驗暨生物技術學系所
  4. Growth arrest dna damage-inducible gene 45 gamma expression as a prognostic and predictive biomarker in hepatocellular carcinoma
 
  • Details

Growth arrest dna damage-inducible gene 45 gamma expression as a prognostic and predictive biomarker in hepatocellular carcinoma

Journal
Oncotarget
Journal Volume
6
Journal Issue
29
Pages
27953-27965
Date Issued
2015
Author(s)
DA-LIANG OU  
Shyue S.-K.
LIANG-IN LIN  
Feng Z.-R.
Liou J.-Y.
Fan H.-H.
Lee B.-S.
CHIUN HSU  
ANN-LII CHENG  
DOI
10.18632/oncotarget.4446
URI
https://scholars.lib.ntu.edu.tw/handle/123456789/502680
Abstract
Growth arrest DNA damage-inducible gene 45 (GADD45) family proteins play a crucial role in regulating cellular stress responses and apoptosis. The present study explored the prognostic and predictive role of GADD45? in hepatocellular carcinoma (HCC) treatment. GADD45? expression in HCC cells was examined using quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. The control of GADD45? transcription was examined using a luciferase reporter assay and chromatin immunoprecipitation. The in vivo induction of GADD45? was performed using adenoviral transfer. The expression of GADD45? in HCC tumor tissues from patients who had undergone curative resection was measured using qRT-PCR. Sorafenib induced expression of GADD45? mRNA and protein, independent of its RAF kinase inhibitor activity. GADD45? induction was more prominent in sorafenib-sensitive HCC cells (Huh-7 and HepG2, IC50 6-7 μM) than in sorafenib-resistant HCC cells (Hep3B, Huh-7R, and HepG2R, IC50 12-15 μM). Overexpression of GADD45? reversed sorafenib resistance in vitro and in vivo, whereas GADD45? expression knockdown by using siRNA partially abrogated the proapoptotic effects of sorafenib on sorafenib-sensitive cells. Overexpression of survivin in HCC cells abolished the antitumor enhancement between GADD45? overexpression and sorafenib treatment, suggesting that survivin is a crucial mediator of antitumor effects of GADD45?. GADD45? expression decreased in tumors from patients with HCC who had undergone curative surgery, and low GADD45? expression was an independent prognostic factor for poor survival, in addition to old age and vascular invasion. The preceding data indicate that GADD45? suppression is a poor prognostic factor in patients with HCC and may help predict sorafenib efficacy in HCC.
SDGs

[SDGs]SDG3

Other Subjects
CCAAT enhancer binding protein; CCAAT enhancer binding protein epsilon; death receptor 5; Fas associated death domain protein; growth arrest and DNA damage inducible protein 45; messenger RNA; protein mcl 1; small interfering RNA; sorafenib; survivin; antineoplastic agent; carbanilamide derivative; CCAAT enhancer binding protein; cell cycle protein; GADD45A protein, human; nicotinamide; nuclear protein; sorafenib; tumor marker; adult; aged; animal experiment; animal model; animal tissue; apoptosis; Article; cancer inhibition; cancer prognosis; cancer resistance; cancer surgery; cancer survival; chromatin immunoprecipitation; clinical article; controlled study; drug efficacy; female; GADD45 gene; gene expression regulation; gene overexpression; gene silencing; human; human cell; human tissue; in vitro study; in vivo study; liver cell carcinoma; luciferase assay; lymph vessel metastasis; male; mouse; nonhuman; outcome assessment; overall survival; predictive value; protein expression; protein function; reverse transcription polymerase chain reaction; survival prediction; survival time; transcription regulation; tumor xenograft; Western blotting; analogs and derivatives; animal; Bagg albino mouse; biosynthesis; drug effects; drug resistance; drug screening; genetic transfection; genetics; Kaplan Meier method; liver cell carcinoma; liver tumor; metabolism; middle aged; mortality; pathology; prognosis; proportional hazards model; tumor cell line; Aged; Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Blotting, Western; Carcinoma, Hepatocellular; CCAAT-Enhancer-Binding Proteins; Cell Cycle Proteins; Cell Line, Tumor; Chromatin Immunoprecipitation; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Mice; Mice, Inbred BALB C; Middle Aged; Niacinamide; Nuclear Proteins; Phenylurea Compounds; Prognosis; Proportional Hazards Models; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Transfection; Xenograft Model Antitumor Assays
Type
journal article

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science