Developing Inhibitors of Ovarian Cancer Progression by Targeted Disruption of the Gamma-Synuclein Activated Migratory and Survival Signaling Pathways
Abstract
Synucleins are a family of highly conserved small proteins that are normally expressed predominantly in neurons. Very little is known about the physiological functions of the synucleins. We have reported that g-synuclein (also known as BCSG1) is dramatically up-regulated in the vast majority (>70%) of late-stage breast and ovarian cancers (Bruening, et al., 2000). When over-expressed, g-synuclein significantly stimulates cell proliferation and metastasis in some breast cancer cell lines. We have shown that DNA hypomethylation is a common mechanism underlying the abnormal expression of this gene in tumor cells (Gupta et al., 2003) and hypothesize that g-synuclein may be a proto-oncogene and that abberant expression of this protein may contribute to the development and progression of ovarian cancer. We also found that g-synuclein can promote cancer cell survival and inhibit stress- and chemotherapy drug-induced apoptosis by modulating MAPKs. Specifically, over-expression of g-synuclein lead to constitutive activation of ERK1/2, and down- regulation of JNK1 in response to a host of environmental stress signals, including Uv, heat shock, sodium arsenate, nitric oxide and chemotherapeutic drugs (Pan, Z-Z, et al., 2002). Because of its high frequency of expression in late- stage ovarian cancers, we hypothesized that g-synuclein may be a promising target for cancer therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA426086
Entities
Organizations
- Fox Chase Cancer Center