Mechanisms of oncogene addiction and tumor recurrence in MYC-induced lymphomas
Abstract/Contents
- Abstract
- Cancers arise through the acquisition of genetic and epigenetic changes which result in the activation of growth-promoting oncogenes and the inactivation of growth-inhibitory tumor suppressor genes. Despite the accumulation of many diverse mutations, some tumors exhibit sensitivity to the targeted inhibition of single gene products, in a phenomenon known as oncogene addiction. In the Emu-tTA/tetO-MYC transgenic mouse model, overexpression of MYC results in the development of aggressive T-cell lymphoma, and subsequent inactivation of MYC results in rapid tumor regression occurring primarily via cell cycle arrest, senescence, and apoptosis. This thesis presents work investigating various aspects of oncogene addiction in MYC-induced lymphomas. We have discovered that tumor recurrence in MYC-induced lymphomas following initial MYC inactivation occurs mainly through the persistence and expansion of cells that fail to suppress MYC expression. This demonstrates that addiction to some oncogenes may be inescapable and that resistance to MYC therapy would likely occur through the restoration of MYC function. We have also discovered that activation of the Wnt/beta-catenin pathway is a common secondary event in MYC-induced lymphomagenesis. Beta-catenin was found to be frequently stabilized due to mutations that prevent its phosphorylation and subsequent degradation, including a novel splice acceptor site mutation. Inhibition of beta-catenin resulted in robust apoptosis, indicating that MYC-induced lymphomas can exhibit addiction to multiple different oncogenes.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Choi, Sok Hyon |
|---|---|
| Associated with | Stanford University, Program in Immunology. |
| Primary advisor | Felsher, Dean (Dean Walton) |
| Thesis advisor | Felsher, Dean (Dean Walton) |
| Thesis advisor | Levy, Ronald, 1941 December 6- |
| Thesis advisor | Martinez, Olivia |
| Thesis advisor | Sage, Julien |
| Advisor | Levy, Ronald, 1941 December 6- |
| Advisor | Martinez, Olivia |
| Advisor | Sage, Julien |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Peter S. Choi. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph. D.)--Stanford University, 2011. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Sok Hyon Choi
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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