Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas

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	Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas
	Miao, J. ; Chen, G. G. ; Yun, J. P. ; Chun, S. Y. ; Zheng, Z. Z. ; Ho, R. L. K. ; Chak, E. C. W. ; Xia, N. S. ; Lai, P. B. S. ; Xia NS(夏宁邵)
刊名	http://dx.doi.org/10.1007/s10495-007-0093-5
	2007-09
关键词	BCL-2 FAMILY-MEMBER BAX-DEPENDENT APOPTOSIS CELL-DEATH EXPRESSION PHOSPHORYLATION HEPATITIS SURVIVAL COMPLEX ROLES GENE
英文摘要	BH3-only protein Bim is a critical regulator of apoptosis and plays an essential role in mammalian development, but the characterization of Bim and its isoforms in hepatocellular carcinoma (HCC) has not been studied before. Here we investigated the expression, distribution, regulation and role of Bim isoforms in HCC cells. Fifteen Bim isoforms were identified in HCC, with six newly identified isoforms and two newly identified exons. Among of them, Bim EL, L, S, a1, a2, a3, b2, b4 and b6 are abundant isoforms according to their mRNA levels. However only Bim EL, L and S proteins could be clearly detected. Bim mRNA and protein were strongly expressed in HCC tissues compared to relevant non-tumorous regions, but the ratio of variant isoforms showed no difference between tumorous and non-tumorous tissues. Bim isoforms were differentially regulated after chemotherapeutic drug 5-Fluorouracil (5-FU) treatment. Interestingly, Bim EL, L and S, the isoforms known to induce apoptosis strongly, are the least inducible isoforms at their mRNA levels when exposed to the stress, suggesting that post-transcriptional rather than transcriptional, modulations may play a role to enhance their functions. Finally, overexpression of Bim EL, L, S and all alpha isoforms induced apoptosis in HCC cells, while overexpression of Bim beta isoforms showed no effects on cell survival after 5-FU treatment. In conclusion, Bim alpha isoforms appears to have a role in the regulation of apoptosis in HCC cells, which may contribute to not only the growth of tumor cells but also the sensitivity of HCC cells to chemotherapy.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65037]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Miao, J.,Chen, G. G.,Yun, J. P.,et al. Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas[J]. http://dx.doi.org/10.1007/s10495-007-0093-5,2007.
APA	Miao, J..,Chen, G. G..,Yun, J. P..,Chun, S. Y..,Zheng, Z. Z..,...&夏宁邵.(2007).Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas.http://dx.doi.org/10.1007/s10495-007-0093-5.
MLA	Miao, J.,et al."Identification and characterization of BH3 domain protein Bim and its isoforms in human hepatocellular carcinomas".http://dx.doi.org/10.1007/s10495-007-0093-5 (2007).