Theses and Dissertations
Date of Award
Master of Science (MS)
Dr. Megan Keniry
Dr. Robert Dearth
Dr. Robert Gilkerson
The PI3K pathway activates AKT, leading to inactivation of FOXO transcription factors. Loss of PTEN results in constitutive inactivation of tumor suppressor FOXO. There is increasing evidence that FOXO resides and promotes transcriptional activity in the nucleus despite high PI3K output within certain advanced cancers and embryonic stem cells. Here, we investigate the regulation and roles of FOXO transcription factors in glioblastoma and basal breast cancer. First, we built and published genetic models to investigate the roles of FOXO transcription factors in cancer cell lines for glioblastoma (U87MG). We examined the function of FOXO transcription factors using these genetic models and found that disruption of FOXO3 led to differentiation and loss of stem cell genes. We also investigated what determines the nuclear localization of FOXO factors in PI3K-activated U87MG cells and found that FOXO4 harbored an in-frame 6 nucleotide insertion that may lead to observed constitutive nuclear localization.
Sanchez, Lilia, "Investigating the Role of Nuclear FOXO3 in PTEN-Null Glioblastomas" (2018). Theses and Dissertations. 382.
Copyright 2018 Lilia Sanchez. All Rights Reserved