Date of Award
8-1-2025
Degree Name
Master of Science
Department
Biological Sciences
First Advisor
Davie, Judy
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and is characterized by disrupted muscle cell differentiation and unchecked proliferation. Among its subtypes, alveolar RMS (ARMS) is especially aggressive and is classically associated with the PAX3-FOXO1 fusion gene, leading to the designation of ARMS as the fusion positive subtype of RMS. The PAX3-FOXO1 fusion activates a host of oncogenic signaling pathways such as PI3K/AKT and the FGF pathway through the direct regulations of Fibroblast Growth Receptor (FGFR4). Our lab has shown that TBX2 is a potent oncogene in RMS which contributes to tumor development by repressing several growth-regulating genes, such as CDKN1A, PTEN, and TP53. In other systems, FGF and the PI3K/AKT pathway have been shown to drive high expression of TBX2, so we sought to investigate how TBX2 is regulated in RMS. This project will explore how upstream signaling events regulate TBX2 expression and the extent to which this affects downstream TP53 activity. We also sought to determine the effect of restoring p53 expression in RMS cells. To do this, a doxycycline-inducible PiggyBac system will be used to reintroduce wild-type TP53 in ARMS cells to test whether restoring its function can reduce proliferation and improve response to therapy. Together, these studies aim to clarify the signaling mechanisms that support RMS progression and identify molecular points of intervention for future treatment strategies.
Access
This thesis is only available for download to the SIUC community. Current SIUC affiliates may also access this paper off campus by searching Dissertations & Theses @ Southern Illinois University Carbondale from ProQuest. Others should contact the interlibrary loan department of your local library or contact ProQuest's Dissertation Express service.