title: Correlation between low-level expression of the tumor suppressor gene TAp73 and the chemoresistance of human glioma stem cells.
abstract: OBJECTIVE
  Glioma stem cells (GSCs) are regarded as the root of glioma growth and recurrence. Chemoresistance is one of the characteristics of GSCs that increases the difficulties in eradicating the cells by anticancer drugs.
  
  
  OBJECTIVE
  The objective of this study is to investigate the correlation between expression of the tumor suppressor gene TAp73 and the chemoresistance of human GSCs.
  
  
  METHODS
  MTT and tumor sphere formation assays were used to analyze the chemoresistance phenotype of GSCs derived from primary human glioma specimens under cisplatin exposure. Reverse transcription real-time PCR was applied for assaying mRNA levels of TAp73. Protein levels of TAp73, p21, Bax, and cleared caspase 3 were assayed by western blot. Cell apoptosis was analyzed by flow cytometry after the annexin V fluorescence staining.
  
  
  RESULTS
  GSCs exhibited increased chemoresistance compared to differentiated glioma cells (DGCs) derived from the same tumor specimen. The expression of TAp73 was lower in GSCs and was not sensitive to cisplatin treatment as compared to DGCs. Overexpression of TAp73 by transfection increased the apoptosis of GSCs in the presence of cisplatin and reduced the chemoresistance of GSC. TAp73 knockdown by siRNA in DGCs reduced cisplatin-induced apoptosis and increased the resistance to cisplatin.
  
  
  CONCLUSIONS
  These findings indicate that TAp73 silencing is hallmark of GSC to maintain their chemoresistance phenotype. Thus, targeting TAp73 may provide a novel strategy to eradicating GSCs.
authors.affiliation: Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Hu
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Xia
authors.forename: Sicang
authors.initials: S
authors.lastname: Yu
authors.forename: Fengjun
authors.initials: F
authors.lastname: Sun
authors.forename: Jianhong
authors.initials: J
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D002945:Cisplatin