小细胞肺癌(SCLC)是肺癌中恶性程度最高的肿瘤，具有早期广泛远处转移的生物学特性,五年生存率仅为3%。本课题组前期研究表明:E2F1在95.7%的SCLC组织中高表达；ADAM12在97.8%的SCLC组织中高表达；干扰E2F1基因表达后, ADAM12表达降低较为显著；推测E2F1有可能通过调控ADAM12的表达参与SCLC浸润转移过程。本研究拟构建含有ADAM12启动子序列及E2F1结合序列突变的荧光素酶表达载体，检测荧光素酶活性，探讨E2F1调控ADAM12表达的分子机制；拟构建沉默ADAM12不同转录本的H1688细胞和稳定表达ADAM12不同转录本的H345细胞，通过体内外实验，观察不同细胞的浸润转移能力，探讨ADAM12不同转录本在SCLC浸润转移中的作用。本课题拟揭示E2F1通过调控ADAM12表达参与SCLC浸润转移的分子机制，为SCLC浸润转移机制的研究提供实验依据。

Small cell lung cancer (SCLC) is the most malignancy tumor in differential pathological lung cancers. With highly invasive characteristic, the five-year survival rate is only 3%. Our previous research showed that E2F1 highly presented in 95.7% SCLC, and the positive expression of ADAM12 was 97.8% in SCLC.When depletion of E2F1 by siRAN targeting E2F1, the expression of ADAM12 was significantly decreased. So, we speculated that E2F1 might participate in the invasion and metastasis by regulating the expression of ADAM12 in SCLC. In present research, the luciferase expression vectors containing the promoter of ADAM12 and the mutant vectors of E2F1 binding sites will be constructed, then transfected into cells and the luciferase activity will be detected. The mechanism of E2F1 regulatting the expression of ADAM12 will be explored. Meanwhile, H1688 cells in which the differential transcripts of ADAM12 will be silenced and H345 cells in which the differential transcripts of ADAM12 will be stable expressed will be constructed. Then the invasion and metastasis of differential group cells will be observed in vivo and in vitro, and the funcion of differential transcripts of ADAM12 will be explored in the process of invasion and metastasis of SCLC. The mechanism of E2F1 participatting in invasion and metastasis by regualting the expression of ADAM12 will be revealed in our prsent research, and our ultimate goal is to provide the experimental basis for clarifying the mechanism about invasion and metastasis of SCLC.