Nagamine K, Shibamoto S, Takeuchi K, Miyazawa K, Kitamura N, Chatani Y, Kohno M, Ito F
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Japan.
Eur J Biochem. 1996 Mar 1;236(2):476-81. doi: 10.1111/j.1432-1033.1996.t01-1-00476.x.
The function of hepatocyte growth factor/scatter factor (HGF/SF) is to increase proliferation as well as to stimulate motility and disperse cell colonies of epithelial cells. In this study, we examined the motogenic and mitogenic responses of two human gastric carcinoma cell types, MKN7 and MKN74. Cell motility of both cell lines was markedly stimulated by HGF/SF. In contrast, HGF/SF stimulated cell growth of MKN74 cells, but did not stimulate growth of MKN7 cells. To address the cause of the difference in response of these cells, which may reflect some differences in signaling pathways downstream from the HGF/SF receptor, c-Met, we investigated the induction of the proto-oncogene c-fos. The level of c-fos mRNA increased and reached a maximum approximately 40 min after HGF/SF stimulation in MKN74 cells, and thereafter its level rapidly decreased. In contrast, the level of c-fos expression was very low irrespective of the stimulation in MKN7 cells. c-Fos protein was transiently induced only in MKN74 cells l h after treatment with HGF/SF, and its levels subsequently decreased. We subsequently examined the activation of mitogen-activated-protein kinase, which is a major mediator in the signaling pathway leading to the stimulation of c-fos transcription, after HGF/SF treatment in both cell lines. Mitogen-activated-protein kinase was markedly activated by this treatment in MKN74 cells, but was only slightly activated in MKN7 cells. These results suggest that although mitogen-activated-protein kinase activation and c-fos induction play an essential role in the signaling pathway leading to cell growth, they are not required for the motility response induced by HGF/SF.
肝细胞生长因子/散射因子（HGF/SF）的功能是增加上皮细胞的增殖，同时刺激其运动并使细胞集落分散。在本研究中，我们检测了两种人胃癌细胞系MKN7和MKN74对HGF/SF的促运动和促有丝分裂反应。两种细胞系的细胞运动均受到HGF/SF的显著刺激。相比之下，HGF/SF刺激了MKN74细胞的生长，但未刺激MKN7细胞的生长。为了探究这些细胞反应差异的原因，这可能反映了HGF/SF受体c-Met下游信号通路的某些差异，我们研究了原癌基因c-fos的诱导情况。在MKN74细胞中，HGF/SF刺激后c-fos mRNA水平升高，并在约40分钟后达到最大值，此后其水平迅速下降。相反，无论是否受到刺激，MKN7细胞中的c-fos表达水平都非常低。c-Fos蛋白仅在HGF/SF处理1小时后的MKN74细胞中短暂诱导表达，随后其水平下降。我们随后检测了丝裂原活化蛋白激酶的激活情况，该激酶是导致c-fos转录受刺激的信号通路中的主要介质，在两种细胞系中进行HGF/SF处理后进行检测。在MKN74细胞中，这种处理显著激活了丝裂原活化蛋白激酶，但在MKN7细胞中仅轻微激活。这些结果表明，尽管丝裂原活化蛋白激酶激活和c-fos诱导在导致细胞生长的信号通路中起重要作用，但它们并非HGF/SF诱导的运动反应所必需。
