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Home » ... » - Faculty » Faculty Pages » Wilding, George |
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Wilding, George
 George Wilding
Professor
Research Area: Prostate carcinogenesis; steroid and growth factor mediated growth control mechanisms; mechanisms of action of cytotoxic agents; drug resistance (chemotherapy agents).
Home Dept: Oncology, School of Medicine and Public Health
Affiliated Depts: Molecular and Environmental Toxicology
Address
Box 2669 Clinical Sciences Center K-4
600 Highland Avenue
Madison, WI 53792
Phone: 608/263-8610 - Email
Research
Androgen Induced Oxidative Stress in Prostate Carcinogenesis
The following is an example of research being performed in Dr. Wilding's laboratory toward identifying key molecular pathways in prostate cancer.
This research examines the effects of androgen, a pivotal regulator of prostate cell growth, on AP-1, a key transcription factor that is diversely involved in molecular signaling pathways that control cellular growth. In these studies, changes in AP-1 activity and AP-1 proteins induced by androgen exposure were determined in the androgen-responsive LNCaP human prostate carcinoma cell line. LNCaP cells were exposed to a growth inhibitory concentration of 1 nM of the androgen R1881 and assayed at early (24 h) and late (96 h) timepoints during the emergence of the androgen-induced growth-inhibition. Androgen exposure produced an increase in AP-1 transcriptional activity from an AP-1-driven reporter vector over 96 h. In addition, AP-1 DNA-binding activity was increased in LNCaP cells exposed to R1881 at 24 and 96 h. Supershift analysis of nuclear extracts from androgen-exposed LNCaP cells showed that both Fra-2 and JunD contributed significantly to the AP-1 DNA-binding complex. The Fra-2 AP-1 factor was detected by a supershift in the AP-1 complex at 24 h. Although Fra-2 mRNA and nuclear protein levels were increased through 96 h of androgen exposure, Fra-2 binding to the AP-1 complex was not observed by supershift analysis at 96 h. Similarly, JunD mRNA levels and a 35 kD form of the JunD protein were increased at 96 h in androgen-treated cells. However, JunD was detected as a significant contributor to the AP-1 complex at both 24 and 96 h in androgen-treated cells as detected by AP-1 complex supershift analysis. This research demonstrates that exposure to growth inhibitory concentrations of androgen significantly modulates AP-1 activity and binding of the AP-1 complex in prostate cells over time, which may be largely due to alterations in the activity of Fra-2 and JunD AP-1 transcription factors.
Dr. Wilding's group continues to investigate the role of androgens in prostate carcinogenesis.
Publications- Kibel AS, Rosenbaum E, Kattan MW, Picus J, Dreicer R, Klein EA, Chatta GS, Nelson JB, DiPaola RS, Roth BJ, Cookson MS, Wilding G, Jarrard DF, Beer TM, Ryan CW, Petrylak DP, Benson MC, Partin AW, Garrett-Mayer E, Eisenberger MA. Adjuvant weekly docetaxel for patients with high risk prostate cancer after radical prostatectomy: a multi-institutional pilot study. J Urol 177(5):1777-81, 2007 May. (Pub Med 17437819)
- Zhang D, Pier T, McNeel DG, Wilding G, Friedl A. Effects of a monoclonal anti-alphavbeta3 integrin antibody on blood vessels - a pharmacodynamic study. Invest New Drugs. 2007 Feb;25(1):49-55. Epub 2006 Sep 26. PMID: 17001523 [PubMed - in process]
- Hussain M, Tangen CM, Higano C, Schelhammer PF, Faulkner J, Crawford ED, Wilding G, Akdas A, Small EJ, Donnelly B, MacVicar G, Raghavan D; Southwest Oncology Group Trial 9346 (INT-0162). Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006 Aug 20;24(24):3984-90. PMID: 16921051 [PubMed - indexed for MEDLINE]
- Messing E, Kim KM, Sharkey F, Schultz M, Parnes H, Kim D, Saltzstein D, Wilding G. Randomized prospective phase III trial of difluoromethylornithine vs placebo in preventing recurrence of completely resected low risk superficial bladder cancer. J Urol. 2006 Aug;176(2):500-4. PMID: 16813878 [PubMed - indexed for MEDLINE]
- Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, Redman BG, Margolin KA, Merchan JR, Wilding G, Ginsberg MS, Bacik J, Kim ST, Baum CM, Michaelson MD. Sunitinib in patients with metastatic renal cell carcinoma. JAMA. 2006 Jun 7;295(21):2516-24. PMID: 16757724 [PubMed - indexed for MEDLINE]
- Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, di'SantAgnese PA, Trump D; Eastern Cooperative Oncology Group study EST 3886. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol. 2006 Jun;7(6):472-9. PMID: 16750497 [PubMed - indexed for MEDLINE]
- Small EJ, Carducci MA, Burke JM, Rodriguez R, Fong L, van Ummersen L, Yu DC, Aimi J, Ando D, Working P, Kirn D, Wilding G. A phase I trial of intravenous CG7870, a replication-selective, prostate-specific antigen-targeted oncolytic adenovirus, for the treatment of hormone-refractory, metastatic prostate cancer. Mol Ther. 2006 Jul;14(1):107-17. Epub 2006 May 9. PMID: 16690359 [PubMed - indexed for MEDLINE]
- Gray R, Manola J, Saxman S, Wright J, Dutcher J, Atkins M, Carducci M, See W, Sweeney C, Liu G, Stein M, Dreicer R, Wilding G, DiPaola RS. Phase II clinical trial design: methods in translational research from the Genitourinary Committee at the Eastern Cooperative Oncology Group. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):1966-9. Review. PMID: 16609005 [PubMed - indexed for MEDLINE]
Check PubMed for other publications by George Wilding
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