|
| Status |
Public on Aug 23, 2012 |
| Title |
Gene-expression profiling of prostate tumors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Increasing evidence suggests that prostate cancer is overdiagnosed and overtreated, and prognostic biomarkers would aid in treatment selection. To define prognostic biomarkers for aggressive prostate cancer, we carried out gene-expression profiling of 98 prostate tumors and 52 benign adjacent prostate tissue samples with detailed clinical annotation. We identified 28 transcripts significantly associated with recurrence after radical prostatectomy including NuSAP, a protein that binds DNA to the mitotic spindle. Elevated NuSAP transcript levels were associated with poor outcome in two independent prostate cancer gene-expression datasets. 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. Posttranscriptional 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 two CCAAT boxes and binding sites for E2F. Transient transfection of an E2F1 cDNA and 431bp of the NuSAP promoter demonstrated E2F1 as an important regulator of expression. Deletion of the E2F-binding site at nucleotide 246 negated the effects of E2F1 on NuSAP expression. Electrophoretic mobility shift assays demonstrated that nuclear extracts of cells overexpressing 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 overexpression appears to be driven in part by E2F1 activation.
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| |
|
| Overall design |
disease_state_design
|
| |
|
| Contributor(s) |
Gulzar Z |
| Citation(s) |
22349817 |
| Submission date |
Aug 21, 2012 |
| Last update date |
Dec 24, 2012 |
| Organization |
Stanford Microarray Database (SMD) |
| E-mail(s) |
array@genome.stanford.edu
|
| Phone |
650-498-6012
|
| URL |
http://genome-www5.stanford.edu/
|
| Department |
Stanford University, School of Medicine
|
| Street address |
300 Pasteur Drive
|
| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
| |
|
| Platforms (4)
|
| GPL9497 |
SMD Print_1529 Homo sapiens |
| GPL15971 |
SMD Print_1392 hos Homo sapiens |
| GPL15972 |
SMD Print_1540 hoaf Homo sapiens |
| GPL15973 |
SMD Print_1564 hoaa Homo sapiens |
|
| Samples (153)
|
|
| Relations |
| BioProject |
PRJNA173433 |
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