在整合基因组微阵列分析系统中发现COP9信号复合体(COP9 signalsome,CSN)的6号亚单位(CSN6) 的扩增。定量PCR分析乳腺癌标本也验证了CSN6的扩增。说明CSN6有作为促进乳腺癌发生发展的癌基因的活性。在检测乳腺癌标本中发现，CSN6高表达的同时PTEN表达降低。同时免疫共沉淀验证CSN6与PTEN 有相互作用。在本研究中，我们将验证CSN6的过表达导致PTEN表达的降低，从而改变乳腺癌细胞的细胞周期，细胞生长等功能。我们将进一步研究CSN6调节PTEN下调的机制，重点验证CSN6促进多聚泛素化PTEN的增加以及MDM2为E3连接酶。通过本课题的研究将进一步揭示出CSN6 在乳腺癌中所起到的癌基因的作用以及对抑癌基因PTEN的下调功能，为乳腺癌发病机制提供理论基础，为乳腺癌的治疗提供新的治疗靶点。

System for Integrative Genomic Microarray Analysis (SIGMA) was employed to evaluate the genetic loss or gain of CSN6 using the data from the BCCRC SMRT arrays.The percentage of cancer cell lines with potential gene amplification of CSN6 (7q22.1) is indicated on a genome karyogram for both breast cancer cells and various other types of cancer cells.CSN6 gene copy number was amplified in a high percentage of primary breast cancer samples.We also found that the expression of PTEN decreased when expression of CSN6 increased in breast cancer samples. There are must be a correlation between the PTEN and CSN6. It is not clear how the CSN6 regulates the downstream genes in the tumorigenesis yet. In this study , we would demonstrate that CSN6 interacts with PTEN and the downregulation of PTEN protein by CSN6 is mediated via proteasome degradation process.We would show that CSN6 could specifically overcome the activity of PTEN to enhance the DNA synthesis, cell survival and cell growth. We would focus on the genetic, biochemical, and functional evidence that the degradation of PTEN is mediated by CSN6 via the proteasome degradation pathway and MDM2 is a potential E3-ligase of PTEN. Our observations would provide a foundation for future efforts to treat breast cancer.