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

细胞表面分子CD 9被认为在信号转导通路或调节细胞活化、发育、增殖和运动中起重要作用，但其确切的生化功能尚不清楚。本研究的目的是确定CD 9表达对细胞增殖和侵袭的影响，这是肿瘤转移和侵袭过程中不可或缺的一步。腺病毒介导的肺腺癌细胞系A549经重组腺病毒介导后，CD 9表达水平呈剂量依赖性增加。细胞增殖实验和碘化丙啶流式细胞仪分析表明，CD 9过表达可诱导细胞周期发生G2/M期阻滞。Western blotting结果表明，G_2/M期阻滞的机制可能与cdc 2/cyclin B复合物的去磷酸化有关。此外，CD 9的过表达抑制MAPK/ERK的磷酸化，表明其参与MAPK信号通路。Boyden小室分析结果表明，CD 9的过表达抑制了肺腺癌细胞的侵袭能力。总之，我们利用腺病毒介导的肺腺癌基因转染，在体外实验中证实了CD 9的表达对肺腺癌细胞增殖和侵袭能力的影响，这是肿瘤转移和侵袭过程中不可或缺的一个环节。

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.