Novel 8OkDa Matrix-Degrading Proteinase in Breast Cancer Invasion and Metasis

摘要

The current project is to study a previously identified breast cancer specific gene, originally designated BCSGl, in human breast cancer progression leading to metastasis. BCSG1, expressed in high abundance in metastatic breast cancer cDNA library but scarcely in normal breast cDNA library, was identified and cloned by differential cDNA sequencing. Interestingly, BCSGl revealed no homology to any other known oncogenes; rather BCSGl revealed extensive sequence homology to Alzheimer disease (AD)-related neurotic proteins synuclein alpha (SNCA) and synuclein beta (SNCB), and thus was also named as synuclein gamma (SNCG). Preliminary studies demonstrated that: (1) SNCG expression was a stage- specific in human breast: undetectable in normal or benign breast lesions, low level and partial expression in low grade ductal carcinoma in situ but extremely, hi h level in advanced infiltrating breast cancer; (2) SNCG expression in human breast cancer cells is dramatically suppressed by tumor growth inhibitor oncostatin M (OM) , a cytokine predominantly produced by activated T cells and macrophages; (3) overexpression of SNCG in breast cancer cells led to a significant increase in cell motility and invasiveness in vitro and a profound augmentation of metastasis in vivo. The overall hypothesis to be evaluated is that SNCG, a neurotic protein mainly expressed in brain and localized to presynaptic terminals, play a critical role in breast cancer malignant progression from benign or non- invasive stage to metastatic stage. In this regard, up-regulation of SNCG will increase cell motility and thus facilitate invasion and metastasis.