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

Using differential cDNA sequencing approach, we first identified a breast cancer specific gene, BCSG1, which was expressed abundantly in metastatic breast cancer cDNA library but scarcely in normal breast cDNA library. Interestingly, BCSG1 revealed no homology to any other known growth factors or oncogenes; rather, BCSG1 revealed extensive sequence homology to neurotic proteins of a synuclein and Beta synuclein, and thus was also named as gamma Synuclein (SNCG). Synucleins are emerging as a central player in the fundamental neural processes and in the formation of pathologically insoluble deposits characteristic of Alzheimer's (AD) and Parkinson's (PD) diseases. However, synucleins particular SNCG have also been implicated in non-neural diseases particularly in the hormone-responsive cancers of breast and ovary. SNCG expression is highly associated with breast cancer and ovarian cancer progression. In addition, overexpression of SNCG in breast cancer cells significantly stimulated cell growth in vitro and tumor metastasis in vivo. However, the molecular targets of SNCG aberrant expression for breast cancer have not been identified. For the first time, we report a chaperone-like activity of SNCG in stimulating the transcriptional activity of estrogen receptor-a (ER-alpha) in MCF-7 cells. Consistent with the stimulation of ER-alpha, SNCG stimulated the ligand-dependent cell proliferation. Demonstration of the stimulation of ER-alpha signaling as one of the cellular functions of SNCG will have a great impact on the biology of steroid receptors and the pathological role of SNCG on hormone-responsive tumors including breast, ovary, and prostate.