Tumor Regression via Over Expession of Transcriptional Factor FOXO3A in Glioblastoma U 87 Cell Type

Graduate #9
Discipline: Biological Sciences
Subcategory: Cancer Research

Charmonix Breann Williams - Jackson State University
Co-Author(s): Kenneth Ndebele, Jackson State University, Jackson, MS

Brain Tumors (Glioblastomas) have tormented society for generations and eluded treatment and strike fear in those affected. Neoplasms or tumors are abnormal masses of tissue that result when cells divide more than they should.

Glioblastomas arise from astrocytes, star shaped supportive tissue of the brain. They are found in the brain and spinal cord. Therapeutic agents targeting glioblastomas have proven to be highly ineffective in clinical settings and disappointing hence, survival is only extended from 2 months to 1 year. This poor prognosis has led to focus on identifying novel molecular targets against glioblastoma and the signaling mechanism through which they act. While many targets are variably expressed in glioblastomas cell lines, the challenge has been to identify those that engage the downstream signaling components in a functional relevant manner, FOXO3a, a member of the forkhead transcription factor family, acts as a tumor suppressor. FOXO3a has been shown to be a critical regulator of the expression of several apoptotic factors such as TNF-Related Apoptosis Inducing Ligand (TRAIL). The functional role of FOXO3a in glioblastomas has not been investigated. To combat this deadly tumor type, we use a genetic approach of over expressing transcriptional factor FOXO3a. We hypothesize that over expression of FOXO3a provides resistance to oxidative stress, halts cell cycle progression, and controls the induction of cellular death in glioblastoma cells, U87.

These studies provide novel insight into the mechanism by which FOXO3a modulates cell transformation and generates effective anti-cancer therapies. We found over expression of FOXO3a induced apoptosis in glioblastoma cell type U-87. Moving forward we have begun to investigate the mechanism of FOXO3a in LN-18 glioblastoma cell type. We expect apoptosis to be induced using the same methodological approach in comparison with U-87 glioblastoma cell type.

Not Submitted

Funder Acknowledgement(s): This research was supported by the Maximizing Access to Research Careers/Undergraduate Student Training in Academic Research (MARC/U-STAR) Program (Grant No. 5T34GM007672-34), National Science Foundation (Grant No. CHE-1156560), and the National Institute of Health (RO1 GM0044931).

Faculty Advisor: Kenneth Ndebele, Kenduma@yahoo.com