AGO2 in overexpression exhibits oncogenic functions KrasG̳1̳2̳D̳ -associated mouse tumor models

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018. === Cataloged from PDF version of thesis. "G̳1̳2̳D̳" in the title on title page appears as superscript. Curriculum Vitae of author on page 2. === Includes bibliographical references. === Cancer is a disease...

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Bibliographic Details
Main Author: Thai, Kevin K. (Kevin Kinh)
Other Authors: Tyler E. Jacks and Phillip A. Sharp.
Format: Others
Language:English
Published: Massachusetts Institute of Technology 2018
Subjects:
Online Access:http://hdl.handle.net/1721.1/115694
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Summary:Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018. === Cataloged from PDF version of thesis. "G̳1̳2̳D̳" in the title on title page appears as superscript. Curriculum Vitae of author on page 2. === Includes bibliographical references. === Cancer is a disease of normal healthy cells that have accumulated genetic aberrations that contribute to uncontrolled cell divisions. Generally, cancer cells have acquired gain of function mutations in oncogenes that positively promote cell proliferation and growth. Simultaneously, mutations in tumor suppressor genes are frequently detected, allowing cells to evade cell cycle checkpoints, resulting in the inhibition of cell death signals. Therefore, identifying genetic abnormalities that promote tumor initiation and progression is imperative in the development of targeted therapeutics. This thesis focuses on the role of Argonaute-2 in promoting cellular transformation in mouse model systems, highlighting novel oncogenic functions associated with AGO2 overexpression. In short, we have determined that AGO2 overexpression promotes metastasis in an autochthonous mouse model of non-small cell lung cancer while elevated AGO2 levels in B cells contribute to the initiation and maintenance of activated B cell-like diffuse large B cell lymphoma (ABC-like DLBCL), both in the context of KRAS activation and Tp53 deletion. === by Kevin K. Thai. === Ph. D.