The Animal Models Core is designed to provide two nnain services. First, the Core will oversee the husbandry, maintenance, and quality control ofthe genetic mouse models of prostate cancer utilized by each Project in the application, including prostate-specific Pten conditional knockout mice (Pterf""""""""'^') and transgenic TRAMP mice. These mouse models are already fully established In the applicants'laboratories, have been properly maintained, and have been used to generate critical preliminary data in support of the various specific aims. As Co-Director of Core B, Dr. Stephen Jones will ensure the maintenance, genotyping, and timely availability of these mouse strains to fulfill the experimental objectives of each Project. The second task of Core B Is to provide state-of-the-art molecular imaging in support of the preclinical evaluation of """"""""network inhibitors"""""""" proposed In the application, which include mitochondria-targeted small molecule Hsp90 inhibitors, Gamitrinibs (Project 1), function-blocking monoclonal antibody (mAb) 6.3G9 to avPe integrin (Project 2), and lentiviral delivery of short hairpin RNA (shRNA) to silence Runx2 in bone metastatic prostate cancer, in vivo (Project 3). For these tasks. Core B will provide quantitative analysis of tumor growth in xenograft studies with genetically engineered prostate cancer cell types, evaluate tumor responses to """"""""network inhibitors"""""""" in localized and metastatic disease models, and map osteoblastic and osteoclastic bone remodeling pathways during intratibial growth of prostate cancer, in vivo. Dr. Alexei Bogdanov, Director of Core B, will lead these efforts by coordinating an extensive portfolio of molecular imaging capabilities, including MRI, (iCT, high resolution X-ray radiography, and bioluminescence. Core B will support equally all three Projects in the application. Overall, these studies will provide a quantitative and unbiased evaluation of prostate cancer responses after treatment with novel molecular therapies, and validate target and pathway specificity, in vivo.

Public Health Relevance

The services provided by Core B are essential to support the preclinical studies of novel molecular therapeutics for advanced prostate cancer as proposed in the application. The synergistic combination of genetic mouse models of prostate cancer, and state-of-the-art molecular imaging will elucidate novel mechanisms of prostate cancer progression, and credential the potential efficacy of network inhibitors as candidate molecular therapies for advanced and metastatic disease In humans.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-0)
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Wistar Institute
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Caino, M Cecilia; Altieri, Dario C (2016) Molecular Pathways: Mitochondrial Reprogramming in Tumor Progression and Therapy. Clin Cancer Res 22:540-5
Lisanti, Sofia; Garlick, David S; Bryant, Kelly G et al. (2016) Transgenic Expression of the Mitochondrial Chaperone TNFR-associated Protein 1 (TRAP1) Accelerates Prostate Cancer Development. J Biol Chem 291:25247-25254
Lu, Huimin; Wang, Tao; Li, Jing et al. (2016) αvβ6 Integrin Promotes Castrate-Resistant Prostate Cancer through JNK1-Mediated Activation of Androgen Receptor. Cancer Res 76:5163-74
Languino, Lucia R; Singh, Amrita; Prisco, Marco et al. (2016) Exosome-mediated transfer from the tumor microenvironment increases TGFβ signaling in squamous cell carcinoma. Am J Transl Res 8:2432-7
Chae, Young Chan; Vaira, Valentina; Caino, M Cecilia et al. (2016) Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming. Cancer Cell 30:257-72
Singh, Amrita; Fedele, Carmine; Lu, Huimin et al. (2016) Exosome-mediated Transfer of αvβ3 Integrin from Tumorigenic to Nontumorigenic Cells Promotes a Migratory Phenotype. Mol Cancer Res 14:1136-1146
Farina, Nicholas H; Zingiryan, Areg; Akech, Jacqueline A et al. (2016) A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice. Oncotarget :
Chae, Young Chan; Angelin, Alessia; Lisanti, Sofia et al. (2015) Corrigendum: Landscape of the mitochondrial Hsp90 metabolome in tumours. Nat Commun 6:7605
Zhang, Xuhui; Akech, Jacqueline; Browne, Gillian et al. (2015) Runx2-Smad signaling impacts the progression of tumor-induced bone disease. Int J Cancer 136:1321-32
Forno, Irene; Ferrero, Stefano; Russo, Maria Veronica et al. (2015) Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression. PLoS One 10:e0130060

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