Fu Yigong, Zagozdzon Radoslaw, Avraham Ron, Avraham Hava Karsenty
Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Int J Oncol. 2006 Dec;29(6):1453-8.
Among the most important signaling pathways operating in pancreatic cancer cells are those resulting from mutations in the Ras oncogene or from overexpression of ErbB-2 and associated Src-family kinases. In this study, we aimed to characterize CHK expression and function in pancreatic cancer. Our data demonstrated CHK expression in human pancreatic cancer tissues, and also showed that CHK associated with ErbB-2 via its SH2 domain in human PANC-1 pancreatic cancer cells. PANC-1 cells were found to express both Src kinase and Lyn kinase, although the expression of Lyn kinase was more abundant. Furthermore, CHK downregulated Lyn kinase activity and significantly inhibited the in vitro growth and invasion of PANC-1 cells upon EGF stimulation. These results indicate that CHK is a negative regulator of ErbB-2 and Lyn kinase signaling in pancreatic cancer cells.
在胰腺癌细胞中发挥作用的最重要的信号通路中，有一些是由Ras癌基因的突变或ErbB-2及相关Src家族激酶的过表达所导致的。在本研究中，我们旨在表征CHK在胰腺癌中的表达和功能。我们的数据证明了CHK在人胰腺癌组织中的表达，并且还表明在人PANC-1胰腺癌细胞中，CHK通过其SH2结构域与ErbB-2相关联。发现PANC-1细胞同时表达Src激酶和Lyn激酶，尽管Lyn激酶的表达更为丰富。此外，CHK下调了Lyn激酶的活性，并在EGF刺激后显著抑制了PANC-1细胞的体外生长和侵袭。这些结果表明，CHK是胰腺癌细胞中ErbB-2和Lyn激酶信号传导的负调节因子。
