Possible involvement of p21/waf1 in the growth inhibition of HepG2 cells induced by hepatocyte growth factor
Possible involvement of p21/waf1 in the growth inhibition of HepG2 cells induced by hepatocyte growth factor
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p21/waf1可能参与肝细胞生长因子诱导的HepG2细胞的生长抑制
DOI：
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发表时间：
1998
影响因子：
5.6
通讯作者：
G. Michalopoulos
中科院分区：
文献类型：
--
作者：
N. Shima;D. Stolz;M. Miyazaki;E. Gohda;K. Higashio;G. Michalopoulos
肝细胞生长因子（HGF）是多种细胞类型的一种有效的有丝分裂原，但它也被称为几种类型肿瘤细胞系的抗丝分裂因子。HGF抑制肿瘤细胞生长的生物学过程仍然知之甚少。在这里，我们报道了一项HGF介导的信号转导事件在两种相反类型的人肝母细胞瘤细胞系HuH6和HepG2之间的比较研究。血清饥饿后，两种细胞系在肝细胞生长培养基（HGM）中培养，HGM是一种化学定义的培养基，存在或不存在HGF。在这些培养条件下，HGF促进HuH6细胞的生长，而抑制HepG2细胞的生长。在HGF刺激后的10分钟内，两种细胞系都观察到p42/有丝分裂原活化蛋白（MAP）激酶的磷酸化。2小时后，HuH6中磷酸化的MAP激酶水平下降到基础水平。然而，在HepG2中，6小时可检测到磷酸化形式。p21/waf1在两种细胞系中均被诱导，其水平在HGF刺激后4-6小时达到峰值。在HuH6中，p21/waf1在8-12小时明显下降，而在HepG2中p21/waf1的高水平持续至少24小时。HGF处理在HepG2中以时间依赖性的方式抑制cdk2活性，而在HuH6中活性增加。当血清饥饿的HepG2在存在或不存在HGF的情况下用血清刺激生长时，HGF处理的细胞发生生长抑制，与p21/waf1的持续诱导和cdk2活性的降低相关。免疫沉淀分析显示cdk2相关的p21/waf1在HGF处理的HepG2中积累。总之，结果表明，在HGF存在的情况下，持续诱导p21/waf1介导HepG2的生长抑制。j .细胞。中国生物医学工程学报（英文版）。©1998 Wiley‐Liss, Inc。
Hepatocyte growth factor (HGF) is a potent mitogen for a variety of cell types, but it is also known as an antimitogenic factor for several types of tumor cell lines. The biological processes by which HGF inhibits tumor cell growth remain poorly understood. Here we report a comparative study of HGF‐mediated signal transduction events between two opposite responding types of human hepatoblastoma cell lines, HuH6 and HepG2. Following serum starvation, both cell lines were cultured in hepatocyte growth medium (HGM), a chemically defined medium, in the presence or absence of HGF. Under these culture conditions, cell growth in HuH6 was promoted by HGF, while it was inhibited in HepG2. Phosphorylation of p42/mitogen‐activated protein (MAP) kinase was observed within 10 min after HGF stimulation in both cell lines. The level of phosphorylated MAP kinase in HuH6 declined to basal levels after 2 hr. However, in HepG2 the phosphorylated form was detectable at 6 hr. p21/waf1 was induced in both cell lines where levels peaked 4–6 hr after HGF stimulation. In HuH6, a marked decrease of p21/waf1 was observed at 8–12 hr, while a high level of p21/waf1 was sustained for at least 24 hr in HepG2. HGF treatment depressed cdk2 activity in a time‐dependent manner in HepG2 while the activity increased in HuH6. When serum‐starved HepG2 was growth stimulated with serum in the presence or absence of HGF, the cells treated with HGF underwent growth inhibition correlating with a sustained induction of p21/waf1 and a decrease of cdk2 activity. Immunoprecipitation analysis revealed accumulation of cdk2‐associated p21/waf1 in the HGF‐treated HepG2. Together, the results suggest that sustained induction of p21/waf1 mediates growth inhibition in HepG2 in the presence of HGF. J. Cell. Physiol. 177:130–136, 1998. © 1998 Wiley‐Liss, Inc.
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影响因子：
8
作者：
Ruth Halaban;Jeffrey S. Rubin;Yoko Funasaka;Melanie H. Cobb;Teri G. Boulton;D. Faletto;Eliot M. Rosen;Andrew Chan;Karen Yoko;W. White;Christopher Cook;Gisela Moellmann
通讯作者：
Ruth Halaban;Jeffrey S. Rubin;Yoko Funasaka;Melanie H. Cobb;Teri G. Boulton;D. Faletto;Eliot M. Rosen;Andrew Chan;Karen Yoko;W. White;Christopher Cook;Gisela Moellmann
影响因子：
10.5
作者：
POLYAK, K;KATO, JY;KOFF, A
通讯作者：
KOFF, A
DOI：
10.1016/s0021-9258(18)82362-6
发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Davis
通讯作者：
R. Davis
影响因子：
4.7
作者：
LIU, ML;MARS, WM;MICHALOPOULOS, GK
通讯作者：
MICHALOPOULOS, GK
影响因子：
3.9
作者：
Lesiow, Monika Katarzyna;Bienko, Alina;Ptaszynska, Natalia
通讯作者：
Ptaszynska, Natalia