Transgenic mouse models provide the possibility to study cancer progression in vivo in a controlled, experimentally manipulable manner. The Myc oncogene is deregulated in a wide range of human cancers, and its activity is often associated with highly aggressive tumor behavior. Myc is a transcription factor that regulates the expression of several thousand genes both directly and through its effects on chromatin structure. Further, Myc is a key factor in induced pluripotency whereby fully differentiated cells can be converted to a pluripotent state by provision of four reprogramming factors (Sox2, Nanog, Oct4, and Myc). Although expression of Myc is required at various stages for correct development of normal hematopoietic lineages, this occurs under strict regulatory constraints. Sustained inappropriate over-expression of Myc leads, in many cases, to tumorigenesis. We have previously studied the ability of Myc to induce tumors in liver, osteosarcoma, and T-cell lymphoma transgenic mouse models. Here, we will focus on analysis of Myc-induced lymphomas, synergistically with our study of human lymphoid and myeloid malignancy. Our mouse model will enable us to analyze induction of self-renewal programs leading to tumor formation, in a controlled context with a specific mechanism of action (Myc over-expression). Using this system, we can also cause tumors to regress and then relapse, permitting analysis of the latter phenomenon and how it relates to cell states. Further, by manipulating genes such as P53, PI 6, Bim inactivation we will perturb processes of apoptosis and senescence to determine their effects on tumor onset and regression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA149145-05
Application #
8628780
Study Section
Special Emphasis Panel (ZCA1-SRLB-C)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2014
Total Cost
$143,119
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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