Term of Award

Summer 2021

Degree Name

Master of Science in Biology (M.S.)

Document Type and Release Option

Thesis (open access)

Copyright Statement / License for Reuse

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Department

Department of Biology

Committee Chair

Dongyu Jia

Committee Member 1

Vinoth Sittaramane

Committee Member 2

Scott Harrison

Abstract

The large number of conserved molecular and signaling pathways between Drosophila melanogaster and humans, makes Drosophila an effective model organism to better understand human diseases, including cancers. Previous studies by clinicians and researchers have identified PTEN, BRCA2, P53, NF1, and RB1 as key mutational drivers in High Grade Serous Ovarian Cancer (HGSOC), the most malignant form of ovarian cancer in humans. The objective of this study was to develop a tumor model in the follicle cell epithelium of the Drosophila ovary and to use immunohistochemistry to study the molecular mechanisms behind tumor development. First, the Drosophila homologs (p53, Brca2, rbf1, Nf1 and Pten) of the key genes in HGSOC and the GAL4/UAS GAL80ts system were used to test the effects of individual silencing of key HGSOC genes on follicle cell epithelial formation. We hypothesized that individually silencing key genes would lead to mild epithelial deformation within the follicle cell epithelium of the Drosophila ovary. Second, we tested the effects of gradually increasing the number of key genes that were silenced on tumor development in the Drosophila ovary using multiple target transgenic RNAi lines and the GAL4/UAS GAL80ts system. We hypothesized that accumulations of silenced genes would lead to the development of a robust tumor-like phenotype in the follicle cell epithelium of the Drosophila ovary. Both hypotheses were confirmed, and a tumor-like phenotype developed in the follicle cell epithelium when all five key genes were silenced. Following the development of the tumor model in the Drosophila ovary, antibody staining of PH3, Armadillo, and Broad, was used to determine if disruptions in molecular and signaling pathways led to tumor formation in the follicle cells. We hypothesized that disruptions in cell/cycle transitions, cell polarity, and cell proliferation would lead to the tumorigenesis of the follicle cells. Consistent with my hypothesis, the follicle cells with the tumor phenotype were caused by these disruptions. The knowledge gained from discovering how key genes cause tumor phenotypes within Drosophila, can potentially lead to cost efficient methods that aid in the development of therapeutic drugs to treat human ovarian cancer.

Research Data and Supplementary Material

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