The Core will perform two major functions: We will assist with the generation and analysis of xenograft tumor models, and generate novel genetically engineered mouse models for prostate tumorigenesis. The generation and analysis of xenografts tumor models is time consuming and requires specific technical expertise. We will provide technical assistance and training to facilitate the use of xenograft models. A major bottle-neck in the testing and generation of better mouse models of prostate cancer is combining standard genetic models with specific additional mutations. We will generate experimental animals in the Core, thereby removing much ofthe initial burden of complex transgenic experiments from the individual Projects within this Program. This will facilitate the use of such genetic models, and will minimize cost and delays due to lack of access to genetic models and lack of resources. Specifically, in support of the Aims of the three Projects within the Program we will: 1) Provide technical support and training for in vivo xenograft experiments and tumor imaging. Members ofthe Core will be involved in the planning and initiation of xenograft experiments, and will assist with in vivo imaging, induding Xenogen imaging and X-ray imaging of metastases to bone. 2) Generate novel combinations of genetic alterations in mice to address roles in prostate tumorigenesis. We will combine novel conditional mutations in Rala and Ralb with prostate specific deletion of the Pten tumor suppressor. Additionally, we will analyze a series of prostate specific PKN1 transgenes, and combine the most informative with a transgene in which constitutively active AKT1 is expressed in the prostate. 3) Generate mice with a targeted Pkn1 conditional null allele. Mice will be generated from ES cells with a targeted conditional mutation in the Pkn1 gene, and prostate-specific deletion of Pkn1 will be combined with the Pten null mutation, 4) Transfer transgenic prostate tumor models to a pure FVB strain background. All mutations will be transferred to a pure FVB strain background to simplify the analysis of prostate specific tumor phenotypes. By providing these services, we will allow the Program to begin to analyze prostate cancer progression more effectively using animal models.
Prostate cancer is the second leading cause of deaths due to cancer in men in the US. The PTEN gene is a frequently mutated tumor suppressor, and deletions or mutation in PTEN are observed in 30% of primary human prostate cancers, as well as more than 60% of prostate metastases. We will generate novel transgenic prostate cancer models that test the role of the PTEN signaling pathway in prostate cancer progression, and analyze prostate tumor progression in vivo.
| Kuscu, Canan; Kumar, Pankaj; Kiran, Manjari et al. (2018) tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 24:1093-1105 |
| Hao, Yi; Bjerke, Glen A; Pietrzak, Karolina et al. (2018) TGF? signaling limits lineage plasticity in prostate cancer. PLoS Genet 14:e1007409 |
| Yang, Chun-Song; Melhuish, Tiffany A; Spencer, Adam et al. (2017) The protein kinase C super-family member PKN is regulated by mTOR and influences differentiation during prostate cancer progression. Prostate 77:1452-1467 |
| Kumar, Pankaj; Kuscu, Canan; Dutta, Anindya (2016) Biogenesis and Function of Transfer RNA-Related Fragments (tRFs). Trends Biochem Sci 41:679-689 |
| Agarwal, Neeraj; Dancik, Garrett M; Goodspeed, Andrew et al. (2016) GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis. Cancer Res 76:5175-85 |
| Reon, Brian J; Dutta, Anindya (2016) Biological Processes Discovered by High-Throughput Sequencing. Am J Pathol 186:722-32 |
| Sakurai, Kouhei; Reon, Brian J; Anaya, Jordan et al. (2015) The lncRNA DRAIC/PCAT29 Locus Constitutes a Tumor-Suppressive Nexus. Mol Cancer Res 13:828-38 |
| Dillon, Laura W; Kumar, Pankaj; Shibata, Yoshiyuki et al. (2015) Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity. Cell Rep 11:1749-59 |
| Kumar, Pankaj; Mudunuri, Suresh B; Anaya, Jordan et al. (2015) tRFdb: a database for transfer RNA fragments. Nucleic Acids Res 43:D141-5 |
| Earl, Julie; Rico, Daniel; Carrillo-de-Santa-Pau, Enrique et al. (2015) The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies. BMC Genomics 16:403 |
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