| dc.identifier.uri | http://hdl.handle.net/11401/76488 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | The functional loss of PTEN through mutations, deletions, or protein degradation has been found at a high frequency in many human cancers. Therefore, the Pten gene locus has been targeted to generate clinically relevant mouse models for metastatic prostate cancer. The first two chapters include the development and exploration of RapidCaP, a novel mouse model for prostate cancer metastasis, that is based on surgical gene transfer to overcome the need for extensive animal breeding. Through prostate specific delivery of transgenic virus, model generation times have been reduced from several years to a few weeks. Moreover, non-invasive Xenogen-based imaging can be used to monitor disease progression. Using RapidCaP, it is shown that focal loss of Pten and Trp53 genes in prostate triggers distant metastasis at 56% penetrance by 4 months. Molecular pathology analysis revealed spontaneous Myc activation in metastatic nodules. Importantly, it was confirmed that Myc can induce local metastasis using a Myc-transgenic RapidCaP model. This demonstrates the identification and functional validation of the system. In castration therapy trials, both primary and metastatic disease respond with regression, but later relapse to produce lethal, castration resistant disease, as seen in human. The RapidCaP system thus introduces a fast and faithful platform for research and therapy of metastatic prostate cancer in genetically engineered mice. The last chapter presents the generation of a dual color reporter system for identification of the regulators of PTEN stability. Taken together, this thesis introduces novel tools for cancer discovery and their application for understanding prostate metastasis. | |
| dcterms.available | 2017-09-20T16:50:24Z | |
| dcterms.contributor | Mills, Alea | en_US |
| dcterms.contributor | Trotman, Lloyd C | en_US |
| dcterms.contributor | Joshua-Tor, Leemor | en_US |
| dcterms.contributor | Vakoc, Christopher | en_US |
| dcterms.contributor | Lowe, Scott. | en_US |
| dcterms.creator | Cho, Hyejin | |
| dcterms.dateAccepted | 2017-09-20T16:50:24Z | |
| dcterms.dateSubmitted | 2017-09-20T16:50:24Z | |
| dcterms.description | Department of Molecular and Cellular Biology. | en_US |
| dcterms.extent | 143 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76488 | |
| dcterms.issued | 2015-08-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:50:24Z (GMT). No. of bitstreams: 1
Cho_grad.sunysb_0771E_11457.pdf: 10322198 bytes, checksum: 51c7e51d13e19c35e3e4cae002a99ab7 (MD5)
Previous issue date: 2013 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Molecular biology | |
| dcterms.subject | Castration, Metastasis, Prostate, PTEN, RapidCaP, Therapy | |
| dcterms.title | RapidCaP, a mouse model for analysis and therapy of prostate cancer reveals drivers of Pten-mutant metastasis. | |
| dcterms.type | Dissertation | |
