FBI-1 promotes cell proliferation and enhances resistance to chemotherapy of hepatocellular carcinoma in vitro and in vivo

被引:37
作者
Fang, Feng [1 ]
Yang, Lianyue [1 ]
Tao, Yiming [1 ]
Qin, Wei [1 ]
机构
[1] Cent S Univ, Xiangya Hosp, Dept Surg, Liver Canc Lab, Changsha 410008, Hunan, Peoples R China
基金
国家高技术研究发展计划(863计划); 中国国家自然科学基金;
关键词
FBI-1; hepatocellular carcinoma; prognosis; chemotherapy; 5-fluorouracil; doxorubicin; p53; p21; p27; PRIMARY LIVER-CANCER; HEPATIC RESECTION; REPRESSES TRANSCRIPTION; MOUSE MODELS; POZ DOMAIN; HEPATOCARCINOGENESIS; PROTEIN; GENE; P53; METASTASIS;
D O I
10.1002/cncr.26251
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: The so-called factor that binds to inducer of short transcripts-1 (FBI-1) purportedly plays an important role in tumorigenesis; however, its role in hepatocellular carcinoma (HCC) remains unknown. The objective of this study was to investigate the expression level, clinical relevance, and biologic function of FBI-1 in HCC. METHODS: Real-time quantitative reverse transcriptase-polymerase chain reaction analysis, Western blot analysis, and immunohistochemical staining were used to detect expression levels of FBI-1 and to analyze its relation to clinicopathologic parameters and to the prognosis of patients with HCC. In addition, the biologic functions of FBI-1 in regulating cell proliferation, migration, and reaction to chemotherapy were detected by using HepG2 cells and SMMC-7721 cells; subsequently, the molecular mechanism of FBI-1 also was investigated. Finally, a xenograft mouse model was used to validate the observations obtained from in vitro studies. RESULTS: Expression levels of FBI-1 messenger RNA and protein were elevated significantly in HCC tissues compared with adjacent nontumorous liver tissues (ANLTs). Increased FBI-1 expression was correlated with multiple tumor nodes, Edmondson-Steiner grade, and a poor prognosis in patients with HCC (P <.05). In vitro studies revealed that FBI-1 was capable of promoting cell proliferation (but not cell migration) by regulating the cell cycle regulation proteins p53, p21, and p27. In addition, FBI-1 could inhibit cell death induced by 5-fluorouracil or doxorubicin through suppressing the activation of p53. Consistent with the in vitro data, FBI-1 was capable of promoting cell proliferation and enhancing chemotherapy resistance of HCC in vivo. CONCLUSIONS: The current findings indicated that FBI-1 plays an important role in HCC carcinogenesis and chemotherapy tolerance, and FBI-1 may served as a novel prognostic marker and therapeutic target for HCC. Cancer 2012; 118: 134-46. (C) 2011 American Cancer Society.
引用
收藏
页码:134 / 146
页数:13
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