Theses and Dissertations

Date of Award

12-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Megan Keniry

Second Advisor

Dr. Robert Gilkerson

Third Advisor

Dr. Michael Persans

Abstract

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.

Comments

Copyright 2022 Shania Pintor. All Rights Reserved.

https://go.openathens.net/redirector/utrgv.edu?url=https://www.proquest.com/dissertations-theses/foxo-factors-regulate-expression-canonical-wnt/docview/2802176607/se-2?accountid=7119

Available for download on Sunday, April 13, 2025

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