A Novel Diagnostic and Therapeutic Marker for Prostate Cancer
Abstract
We have identified a novel protein, SSeCKS (pronounced essex), which is a major substrate of Protein Kinase C (PKC) and tyrosine kinases that plays a key scaffolding role at the juncture of cytoskeletal architecture and proliferative signaling pathways. In untransformed prostate epithelial cells, SSeCKS transcription and protein phosphorylation are cell-cycle regulated, and in many oncogenically-transformed cells, SSeCKS is hyperphosphorylated on select serine and tyrosine residues. We have analyzed whether SSeCKS plays a role in prostate cancer biology. Our current data indicate that SSeCKS is downregulated at the RNA and protein levels in typically studied human prostate cancer cell lines and in undifferentiated (i.e. - advanced) prostate cancers in humans. We have also produced and characterized two monoclonal antibodies specific for PKC phosphorylated regions on SSeCKS. We are attempting to adapt these reagents as diagnostic tools for prostate cancer progression. Lastly, we have produced rat MatLyLu prostate cancer cells with tetracycline-regulated SSeCKS re-expression. Our data indicate that SSeCKS inhibits anchorage-independent growth in vitro, and in an athymic mouse model, SSeCKS severely inhibits the appearance of lung metastases. Our data strongly suggest that SSeCKS functions as a suppressor of metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2000
- Accession Number
- ADA384862
Entities
People
- Irwin H Gelman
Organizations
- Icahn School of Medicine at Mount Sinai