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FBI-1 promotes cell proliferation and enhances resistance to chemotherapy of hepatocellular carcinoma in vitro and in vivo
Article first published online: 28 JUN 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 1, pages 134–146, 1 January 2012
How to Cite
Fang, F., Yang, L., Tao, Y. and Qin, W. (2012), FBI-1 promotes cell proliferation and enhances resistance to chemotherapy of hepatocellular carcinoma in vitro and in vivo. Cancer, 118: 134–146. doi: 10.1002/cncr.26251
- Issue published online: 16 DEC 2011
- Article first published online: 28 JUN 2011
- Manuscript Accepted: 15 APR 2011
- Manuscript Revised: 14 APR 2011
- Manuscript Received: 29 SEP 2010
- hepatocellular carcinoma;
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.
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.
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.
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;. © 2011 American Cancer Society.