Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Theses and Dissertations
  • Duke Dissertations
  • View Item
  •   DukeSpace
  • Theses and Dissertations
  • Duke Dissertations
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Investigating the Fate of Pre-neoplastic Cells in a Mouse Model of Medulloblastoma

Thumbnail
View / Download
2.9 Mb
Date
2009
Author
Kessler, Jessica Dawn
Advisor
Wechsler-Reya, Robert J
Repository Usage Stats
642
views
637
downloads
Abstract

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.

Type
Dissertation
Department
Molecular Cancer Biology
Subject
Biology, Molecular
granule cell precursors
medulloblastoma
patched
pre
neoplastic lesions
Permalink
https://hdl.handle.net/10161/1186
Citation
Kessler, Jessica Dawn (2009). Investigating the Fate of Pre-neoplastic Cells in a Mouse Model of Medulloblastoma. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/1186.
Collections
  • Duke Dissertations
More Info
Show full item record
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.

Rights for Collection: Duke Dissertations


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University