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FBI‐1 promotes cell proliferation and enhances resistance to chemotherapy of hepatocellular carcinoma in vitro and in vivo
Author(s) -
Fang Feng,
Yang Lianyue,
Tao Yiming,
Qin Wei
Publication year - 2011
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.26251
Subject(s) - cell growth , cancer research , carcinogenesis , in vitro , doxorubicin , in vivo , hepatocellular carcinoma , immunohistochemistry , western blot , cell culture , cell , cell cycle , medicine , blot , biology , chemotherapy , cancer , pathology , gene , biochemistry , genetics , microbiology and biotechnology
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;. © 2011 American Cancer Society.