The mechanism of CD9 and development of gene therapy for lung cancer

细胞表面分子CD9被认为在信号转导途径或细胞活化、发育、增殖和运动的调节中起重要作用，尽管CD9的确切生化功能尚不清楚。本研究的目的是利用腺病毒基因转导体外肺腺癌，明确CD9表达对细胞增殖和侵袭的影响，而细胞增殖和侵袭是肿瘤转移和侵袭过程中不可或缺的一步。用重组Advs孵育人腺癌细胞A549，细胞CD9的表达呈剂量依赖性增加。细胞增殖实验和碘化丙啶流式细胞术细胞周期分析表明，CD9过表达诱导G_2/M阻滞细胞周期。通过western blotting分析，G_2/M阻滞的机制被认为是cdc2/cyclin B复合物的去磷酸化。此外，CD9的过表达抑制了MAPK/ERK的磷酸化，表明参与了MAPK信号通路。博伊登室分析表明，CD9过表达抑制了侵袭细胞的数量。总之，我们在肺腺癌体外实验中利用腺病毒基因转导证实了CD9表达对细胞增殖和侵袭的影响，而细胞增殖和侵袭是肿瘤转移和侵袭过程中不可或缺的一步。

The cell-surface molecule CD9 were thought to play an important role in signal transduction pathways or in the regulation of cell activation, development, proliferation, and motility, although the precise biochemical functions of CD9 remain unknown.The purpose of this study is to define the effects of CD9 expression on cell proliferation and invasion, which is an integral step in the process of tumor metastasis and invasion, using adenovirally gene transduction in lung adenocarcinoma in vitro.The human adenocarcinoma cell line A549 was incubated with recombinant Advs, and then cells increased the expression level of CD9 in a dosage-dependent manner. Cell proliferation assay and cell cycle analysis using flow cytometric assay with propidium iodide revealed that over-expression of CD9 induced G_2/M arrest in cell cycle. The mechanism of G_2/M arrest was thought to be dephosphorylation of cdc2/cyclin B complex, using western blotting. Moreover, the over expression of CD9 suppress the phosphorylation of MAPK/ERK, which was indicated participation in MAPK signaling pathway. The analysis using boyden chamber resulted the over expression of CD9 inhibited the number of invasion cells.In conclusion, we have demonstrated the effects of CD9 expression on cell proliferation and invasion, which is an integral step in the process of tumor metastasis and invasion, using adenovirally gene transduction in lung adenocarcinoma in vitro.