Understanding the Repopulation of Glioblastoma in Drosophila Melanogaster Model System
Leah D Bullock, Kirti Snigdha
Glioblastoma Multiforme (GBM) is the most common form of malignant brain tumors, accounting for about 52% of all primary brain tumors. Patients diagnosed with GBM typically die within a few months after diagnosis. Upon initial diagnosis of GBM, standard treatment consists of surgery, radiation therapy, and chemotherapy. GBM has an unfavorable diagnosis due to the high rates of tumor recurrence. The cause of the repopulation of the tumor after treatment is currently unknown. Therefore there is a need to create a simple model system to study the repopulation of GBM. We have created a simple glioma model in Drosophila melanogaster to study the effects of X-ray radiation on tumor size and repopulation of the tumor. We generated the glioma model by suppressing Pten while overexpressing oncogene RasV12 in glial cells of the fly brain to induce tumor. Flies with genotype UASPten RNAi;UASRasV12; Repo Gal4 UASGFP developed aggressive brain tumors and failed to survive to the adult stage. To model repopulation, we standardized the X-ray dosage. We observed that after exposing the 1st instar larvae to 3.5 gy X-ray, there was a significant reduction in tumor size in the larvae compared to the unexposed samples. This revealed effects of X-ray radiation on tumor; however there was still excess of glial population after X-ray treatment as seen in human gliomas too. Hence we have effectively established a glioma repopulation model. We are now looking into the mechanistic details of why X-ray radiation causes reduction in tumor and why repopulation of tumor cells occurs after treatment. Here we report our recent findings. Since most of the signaling pathways are conserved from flies to mammals, these findings can be utilized in other model systems and in humans and opens new avenues for glioma treatment.
Honors Thesis - Graduate
Madhuri Kango-Singh, Amit Singh
Primary Advisor's Department
Stander Symposium project
"Understanding the Repopulation of Glioblastoma in Drosophila Melanogaster Model System" (2017). Stander Symposium Projects. 1111.