Show simple item record

dc.contributor.advisor Wechsler-Reya, Robert J en_US
dc.contributor.author Kessler, Jessica Dawn en_US
dc.date.accessioned 2009-05-01T18:34:49Z
dc.date.available 2009-05-01T18:34:49Z
dc.date.issued 2009 en_US
dc.identifier.uri http://hdl.handle.net/10161/1186
dc.description Dissertation en_US
dc.description.abstract <p>Studying the early stages of cancer can provide important insight into the molecular basis of the disease. In many human cancers, such as prostate, pancreatic, and colon cancer, a pre-neoplastic, or intermediate, stage of the disease has been identified. The pre-neoplastic stage is presumed to be a transition during which normal cells undergo malignant transformation. However, the link between the pre-neoplastic cells and end-stage disease has never been formally established. To investigate the fate of such cells, the patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma was used. Pre-neoplastic cells (PNCs) are found in most ptc mutants during early adulthood, but only 15% of these animals develop tumors. Although PNCs are found in mice that develop tumors, the ability of PNCs to give rise to tumors has never been demonstrated directly, and the fate of cells that do not form tumors remains unknown. Genetic fate mapping and orthotopic transplantation provided definitive evidence that PNCs give rise to tumors and showed that the predominant fate of PNCs that do not form tumors is differentiation. Moreover, N-myc, a gene commonly amplified in medulloblastoma, can dramatically alter the fate of PNCs, preventing differentiation and driving progression to tumors. Importantly, N-myc allows PNCs to grow independently of hedgehog signaling, making the resulting tumors resistant to hedgehog antagonists. These studies provide the first direct evidence that PNCs can give rise to tumors, and demonstrate that identification of genetic changes that promote tumor progression is critical for designing effective therapies for cancer.</p> en_US
dc.format.extent 3023874 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Biology, Molecular en_US
dc.subject granule cell precursors en_US
dc.subject medulloblastoma en_US
dc.subject patched en_US
dc.subject pre en_US
dc.subject neoplastic lesions en_US
dc.title Investigating the Fate of Pre-neoplastic Cells in a Mouse Model of Medulloblastoma en_US
dc.type Dissertation en_US
dc.department Molecular Cancer Biology en_US

Files in this item

This item appears in the following Collection(s)

Show simple item record