Invasiveness of hepatocellular carcinoma cell lines: Contribution of hepatocyte growth factor, c-met, and transcription factor Ets-1
Invasiveness of hepatocellular carcinoma cell lines: Contribution of hepatocyte growth factor, c-met, and transcription factor Ets-1
复制标题
DOI：
10.1006/bbrc.2001.5521
复制
发表时间：
2001-09-07
影响因子：
3.1
通讯作者：
Yang, XM
中科院分区：
文献类型：
--
作者：
Jiang, Y;Xu, WX;Yang, XM
为了解肝细胞癌的侵袭和转移机制，检测了c-met和Ets-1在4种肝癌细胞系中的表达，以及HGF对这些细胞运动和侵袭能力的影响。分析表明，c-met和Ets-1的过表达与肝癌细胞系的运动能力和侵袭能力密切相关。加入HGF可增强HepG2和HLE细胞的侵袭活性。HGF可调节HepG2和Bel-7402细胞中c-met的转录，也可诱导Bel-7402细胞中Ets-1的转录。稳定转导人ETS-1基因的Bel-7402细胞与亲本细胞和模型细胞相比，其侵袭能力显著增强。转染Ets-1的Bel-7402细胞c-Met、MMP1、MMP9和u-PA的表达水平显著升高，并随着c-Met表达的增加而增加。转Ets-1基因的Bel-7402细胞对外源性HGF刺激的侵袭力和运动能力更敏感。此外，Ets-1基因反义寡核苷酸治疗Bel-7402细胞和HLE肝癌细胞的侵袭活性明显降低，并下调Ets-1、c-Met、u-PA、MMP1和MMP9的转录。这些结果有力地提示Ets-1在肝癌细胞侵袭性中起重要作用，可能存在增强肝癌细胞侵袭力的环路。(C)2001年学术出版社。
To understand the mechanism of invasion and metastasis of hepatocellular carcinoma (HCC), the expression of c-met and Ets-1, and the effect of HGF on these cell's motility and invasion ability were examined in four hepatoma cell lines. The analysis revealed that the overexpression of c-met and Ets-1 is closely connected with the motility and invasion ability of the HCC cell lines. Invasion activity of HepG2 and HLE cells were enhanced by the addition of HGF to medium. HGF regulated c-met transcription in HepG2 and Bel-7402 cells, HGF also induced Ets-1 transcription in Bel-7402 cell. Bel-7402 cells stably transduced with the human Ets-1 gene showed significantly increased invasion potentials compared to parental and mock-transfected cells. The expression level of c-met, MMP1, MMP9, and u-PA in Bel-7402 cells transfected with Ets-1 were markedly increased, and as a consequence of c-met expression increase. Bel-7402 cells transfected with Ets-1 were more responsive to exogenous HGF stimulation in invasiveness and motility ability. In addition, conditioned by antisense Ets-1 oligonucleotide-treat-Bel-7402 cells transfected with Ets-1 gene and HLE hepatoma cells showed markedly reduced invasion activity, and down-regulated the transcription of Ets-1, c-met, u-PA, MMP-1, and MMP-9. These results strongly suggest that Ets-1 has a crucial role in the invasive property in hepatoma cell lines, and there may exist a loop to enhance the invasive ability of hepatoma cell lines. (C) 2001 Academic Press.