Role of NuSAP in Prostate Tumor Progression
Abstract
We have identified NuSAP as prognostic marker upregulated in recurrent prostate tumors. Our grant aimed at identifying the role of NuSAP in promoting proliferation and invasion in Prostate Cancer and identify genes that upregulate NuSAP expression. To characterize the role and regulation of NuSAP in prostate cancer, we studied the expression of NuSAP in the LNCaP and PC3 human prostate cancer cell lines. Post-transcriptional silencing of the NuSAP gene severely hampered the ability of PC3 to invade and proliferate in vitro. The promoter region of the NuSAP gene contains 2 CCAAT boxes and binding sites for E2F. Transient transfection of an E2F1 cDNA and 431 bp of the NuSAP promoter demonstrated E2F1 as an important regulator of expression. Deletion of the E2F binding site at nt -246 negated the effects of E2F1 on NuSAP expression. Electrophoretic mobility shift assays demonstrated that nuclear extracts of cells over-expressing E2F1 bound directly to the E2F binding site in the NuSAP promoter region. Finally, immunohistochemistry showed a strong correlation between E2F1 and NuSAP expression in human prostate cancer samples. NuSAP is a novel biomarker for prostate cancer recurrence after surgery and its over-expression appears to be driven in part by E2F1 activation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2012
- Accession Number
- ADA562839
Entities
People
- James D Brooks
Organizations
- Stanford University