Date of Award
Master of Science (MS)
Dr. Megan Keniry
Dr. Robert Gilkerson
Dr. Michael Persans
Basal-like breast cancer (BBC) and Glioblastoma Multiforme (GBM) each express stem gene expression signatures which are partly driven by FOXO transcription factors. Preliminary data from Gene Set Enrichment Analysis (GSEA) with RNA Seq. data indicated that a set of WNT target genes including LEF1, and TCF7 were robustly induced after 48-hours of AS1842856 (FOXO1 inhibitor) treatment. These same genes were also induced in GBM cell lines U87MG, LN18, LN229, A172, and DBTRG upon treatment with AS1842856. In contrast to FOXO1 inhibition, RNAi targeting of FOXO1, led to reduced LEF1, and TCF7 gene expression in BT549 and U87MG cells. Furthermore, CRISPR Cas9-mediated FOXO1 disruption also led to reduced expression of canonical WNT genes in U87MG cells. This work demonstrates that FOXO1 promotes canonical WNT gene expression in examined BBC and GBM cells similar to results found in Drosophila melanogaster and murine AML models.
Pintor, Shania, "Foxo Factors Regulate the Expression of Canonical WNT Target Genes in a Set of Basal-Like Breast and Glioblastoma Multiforme Cancer Cell Lines" (2022). Theses and Dissertations. 1171.
Available for download on Sunday, April 13, 2025