title: Role of 3' repressor sequences of p53 in anti-cancer drug sensitivity of human lung tumor cells.
abstract: BACKGROUND
  The C-terminus of p53 and non-coding mRNAs play critical roles in negative regulation. However, their impact on anti-cancer drug sensitivity remains unclear.
  
  
  METHODS
  In this study, we investigated the effects of p53 deleting these sequences on anti-cancer drug sensitivity by drug sensitivity test, flow cytometry, Agilent mRNA expression microarray detection, transplantation tumor in nude mice.
  
  
  RESULTS
  The results showed that the cell line with p53 deleted the C-terminal sequences (p53(del)) was more sensitive to navelbine (NVB) compared to the cell line that carried the full length p53 (p53(wt)). The p53(del) cells was more sensitive to cisplatin (PDD) and 5-fluorouracil (5FU) than p53(wt) cells but there was not significant difference. NVB treatment led to significant G2 arrest and apoptosis in p53(del) cells but not in p53(wt) cells. mRNA expression profile of p53(del) cells indicated that approximately 11% of the 41,000 genes in genome showed differential expression after NVB treatment, among which 2064 genes were up-regulated and 2784 were down-regulated with fold change >2 (P<0.01). Tumor transplantation assay in nude mice showed that the p53 truncation significantly increased tumor sensitivity to NVB compared to the full-length p53, with 99.46% tumor inhibition.
  
  
  CONCLUSIONS
  In summary, deletion of 37 amino acid residues (356-393) and 3' non-coding mRNAs at the C-terminus of p53 selectively increased tumor sensitivity to the mitotic inhibitor NVB.
authors: Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, China.
authors: Hui
authors: H
authors: Wang
authors: Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, China. Electronic address: li_weiying412@aliyun.com.
authors: Weiying
authors: W
authors: Li
authors: Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, China.
authors: Baitang
authors: B
authors: Lai
authors: Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, China.
authors: Xuehui
authors: X
authors: Yang
authors: Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, China.
authors: Chunyan
authors: C
authors: Zhang
authors: Oncology Department, Beijing Chest Hospital, Capital Medical University, China.
authors: Hong
authors: H
authors: Tao
authors: Oncology Department, Beijing Chest Hospital, Capital Medical University, China.
authors: Yunzhong
authors: Y
authors: Zhu
authors: Institute of Biophysics of Chinese Academy of Sciences, China.
authors: Jinzhao
authors: J
authors: Li
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017384:Sequence Deletion; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014747:Vinblastine; D000077235:Vinorelbine
keywords: 3′ repressor sequences; Drug sensitivity; Lung cancer; p53