Characterization of Novel Breast Cancer Specific Gene, BCSG1, in Human Breast Cancer Progression

There continues to be uncertainty as to whether premalignant lesions that ultimately develop into metastatic breast cancer can be identified histologically. Many of the genetic changes during malignant progression manifest them as alterations in the cellular complement of novel transcribed mRNAs. We have previously reported the isolation of a new breast cancer specific gene BCSGl by differential cDNA sequencing. BCSGl, which was high abundance in a breast cancer cDNA library but scarcely in a normal breast cDNA library, was identified as a putative breast cancer marker. Interestingly, BCSGl revealed no homology to any other known growth factors or oncogenes; rather BCSGl has a great sequence homology with Alzheimer disease (AD)-related neural protein synuclein (SNC) that are mainly expressed in brain, and thus was also named as synuclein gamma (SNCG). The SNCs have primarily been studied as neural proteins, as they are highly expressed in neurons and appear to be involved in the etiology of neurodegenerasive diseases. We demonstrated that 1) SNCG expression is 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 high level in advanced infiltrating breast cancer; 2) overexpression of SNCG in human breast cancer cells leads to a significant increase in motility and invasiveness in vitro and a profound augmentation of metastasis; and 3) expression of SNCG in breast cancer cells is significantly down- regrlated by growth inhibitory cytokine oncostatin M (OM). The knowledge gained from these studies will allow us to target specific pathway contributory to the breast cancer progression. In addition, if overexpression provides a therapeutic target, then BCSGl may be useful in clinical management and treatment of breast cancer.