| Summary: | 碩士 === 國立中興大學 === 生命科學系所 === 99 === Cdk5(Cyclin-dependent kinase 5) belongs to CDK family but does not involve cell cycle regulation. The specific activator of Cdk5 is p35 rather than cyclin. Cdk5/p35 play an important role in nervous system and neurodegenerative disease. In the recent studies, Cdk5/p35 also play an important role in non-neuronal cells including cancer cells. Lung cancer is the leading cause of cancer death in the worldwide. According to the pathological characteristics, lung cancer can be divided into small cell lung cancer and non-small cell lung cancer. Most lung cancer patient are non-small cell lung cancer. According to the previous research, Cdk5/p35 has high expression in non-small cell lung cancer. In addition, single-nucleotide polymorphisms in the promoter of the CDK5 gene contribute to the genetic susceptibility to lung cancer in the Korean population. The mechanism of Cdk5/p35 on cell proliferation and biological function of lung cancer is still unclear. Here we verify the role of Cdk5/p35 in non-small cell lung cancer. The MTT assay results show that Cdk5 or p35 overexpression by transient transfection increased the cell proliferation of A549 cells. On the other hand, knockdown Cdk5 or p35 expression by siRNA could inhibit cell growth and cell migration of A549 cells monitored by wound healing assay. According to the reference published in 2001, ERK induces p35 through induction of Egr-1. ERK is one of the EGFR downstream signal pathways. Here we propose the mechanism of EGFR regulate p35/Cdk5 through ERK/Egr-1 pathway in non-small cell lung cancer. The results show that EGF induces p35 through ERK/Egr-1 pathway in a time-course manner. Cdk5 activity also increased under EGF treatment. Furthermore, the induction of p35 by EGF could be abolished by ERK inhibitor or knockdown Egr-1 by shRNA. The stimulation on cell migration by EGF could be inhibited by knockdown p35 or Egr-1 expression. Taken together, we demonstrate the important of Cdk5/p35 in cell proliferation and cell migration of non-small cell lung cancer. We also demonstrate the regulation of p35/Cdk5 by EGFR through ERK/Egr-1 pathway. Base on these experimental results, we hope to understand the roles of Cdk5/p35 in lung cancer from the view points of basic research. These findings in the future can contribute to the diagnosis and treatment of lung cancer.
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