title: Aberrant expression of the p53-inducible antiproliferative gene BTG2 in hepatocellular carcinoma is associated with overexpression of the cell cycle-related proteins.
abstract: We previously reported that the abnormal BTG2 expression was related to genesis/development of hepatocellular carcinoma (HCC). The aim of this study was to evaluate the BTG2 expression in HCC compared with p53, cyclin D1, and cyclin E. For this purpose, modified diethylnitrosamine (DEN)-induced primary HCC rat model was established. Target proteins and mRNAs were measured by western blot and RT-PCR/northern blot, respectively. In rat liver, expression of BTG2 and other proteins was determined by western blot, and BTG2 mRNA in HCC/normal tissues was detected by high-flux tissue microarray (TMA) and in situ hybridization (ISH). BTG2 mRNA/protein expression was increased in fetal liver, 7701, and LO2 cell lines but decreased in HepG2 cells. BTG2/p53 were expressed early after DEN treatment, peaked at 5 weeks and decreased gradually thereafter. Cyclin-D1/Cyclin-E expression increased significantly with the tumor progression. BTG2 mRNA was expressed in 71.19% HCC by ISH and correlated with differentiation. Expression of p53/cyclin D1/cyclin E was positive in 82.35/94.12/76.47% BTG2 mRNA-negative tissues, respectively. BTG2 protein expression was lost in 32.2% (19/59) HCC tissues, and the mRNA/protein expression correlated significantly with the increasing tumor grade (P < 0.05). In conclusion, BTG2 expression is commonly impaired in HCC which may be a factor involved in deregulation of cyclin-D1/cyclin-E expression during hepatocarcinogenesis.
authors.affiliation: Cancer Center, Institute of Surgical Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.forename: Ge
authors.initials: G
authors.lastname: Wang
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Yang
authors.forename: Jinlu
authors.initials: J
authors.lastname: San
authors.forename: Jijun
authors.initials: J
authors.lastname: Zheng
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.forename: Xizhong
authors.initials: X
authors.lastname: Luo
authors.forename: Qing
authors.initials: Q
authors.lastname: Hu
authors.forename: Zengpeng
authors.initials: Z
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C521959:BTG2 protein, rat; D018797:Cell Cycle Proteins; D019927:Cyclin E; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D004052:Diethylnitrosamine