Investigating the Role of Nuclear FOXO3 in PTEN-Null Glioblastomas

Author

Lilia Sanchez, The University of Texas Rio Grande Valley

Date of Award

7-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Dr. Megan Keniry

Second Advisor

Dr. Robert Dearth

Third Advisor

Dr. Robert Gilkerson

Abstract

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.

Comments

Copyright 2018 Lilia Sanchez. All Rights Reserved.

https://www.proquest.com/dissertations-theses/investigating-role-nuclear-foxo3-i-pten-null/docview/2118658752/se-2?accountid=7119

Recommended Citation

Sanchez, Lilia, "Investigating the Role of Nuclear FOXO3 in PTEN-Null Glioblastomas" (2018). Theses and Dissertations. 382.
https://scholarworks.utrgv.edu/etd/382