MP46-04 REAL TIME IN VIVO MOLECULAR IMAGING OF NF-κB IN PROSTATE CANCER: ROLE AS PROGNOSTIC BIOMARKER AND THERAPEUTIC TARGET

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2015MP46-04 REAL TIME IN VIVO MOLECULAR IMAGING OF NF-κB IN PROSTATE CANCER: ROLE AS PROGNOSTIC BIOMARKER AND THERAPEUTIC TARGET Eugene Vykhovanets, Sanjeev Shukla, Eswar Shankar, Olena Vykhovanets, Gregory MacLennan, and Sanjay Gupta Eugene VykhovanetsEugene Vykhovanets More articles by this author , Sanjeev ShuklaSanjeev Shukla More articles by this author , Eswar ShankarEswar Shankar More articles by this author , Olena VykhovanetsOlena Vykhovanets More articles by this author , Gregory MacLennanGregory MacLennan More articles by this author , and Sanjay GuptaSanjay Gupta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1567AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The transcription factor NF-κB is broadly associated with oncogenesis through its ability to control cell proliferation and to suppress apoptosis. Aberrant NF-κB activation has been observed in various human malignancies including prostate cancer. Clinical studies demonstrate higher expression of NF-κB family members: p65/RelA, p50/RelB, and cRel in primary prostate cancer specimens and in metastatic tumors which correlate with poor survival. While NF-κB is considered to play a key role in prostate cancer progression, its value as prognostic marker and therapeutic target has not been elucidated. Through development of new in vivo model and real-time imaging, we established the relevance of NF-κB as a bio-marker and therapeutic target in prostate cancer. METHODS Crossbreeding of NF-κB-Luc Tag mice and TRAMP (transgenic adenocarcinoma mouse prostate) provide bi-transgenic offspring (LucTg/TRAMPTg mice) for the study. Noninvasive in vivo and ex vivo bioluminescence imaging of NF-κB activation and prostate cancer progression was followed for 40 weeks in these mice. For therapeutic relevance, 12 weeks old NF-κB-Luc Tag mice and bi-transgenic mice were gavaged with parthenolide (10 mg/kg), an NF-κB inhibitor for 5 days/week for 8 weeks. Whole body NF-κB activity was performed every 2 weeks, while ex-vivo NF-κB activity in the GU complex, thymus, spleen, bladder and prostate gland was determined after 8 weeks. To analyze the role of NF-κB in metastasis, mice were subjected to surgical castration followed by measurement of NF-κB activity. Western blotting was used to determine the expression of NF-κB family members, its upstream and downstream targets in the dorsal-lateral prostate. RESULTS Age-dependent cancer progression was observed in the prostate which positively correlated with NF-κB activation. Ex vivo analysis showed increased NF-κB activity in the dorsal-lateral prostate with concurrent increase in tumor progression. Parthenolide treatment blocked NF-κB activity in the prostate; preserved gross anatomy, shape and size of the GU complex; and tumor regression as evident by decrease in p65/RelA, p50/RelB, PCNA and phosphorylation of IκBα. Initial castration of mice decreased NF-κB activity in the prostate; whereas 67% of the castrated mice exhibited increase in NF-κB activity 2 weeks after castration which correlated with tumor recurrence and poor survival. CONCLUSIONS Our findings demonstrate real-time NF-κB imaging in a pre-clinical model and establishes its potential as prognostic marker and therapeutic target in prostate cancer. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e545 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eugene Vykhovanets More articles by this author Sanjeev Shukla More articles by this author Eswar Shankar More articles by this author Olena Vykhovanets More articles by this author Gregory MacLennan More articles by this author Sanjay Gupta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...