Presenter(s)

    Venolia Adjei, Sydney Ellen Anderson, Brandon Jericho Clark, Maria Theresa El Biri, Michael K. Gruhot

    Comments

    Presentation: 10:45-12:00, Kennedy Union Ballroom

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    Description

    Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the US, with the American Cancer Society estimating 153,000 new diagnoses and 53,000 deaths in 2023. Genetic mutations in the genes Ras, APC, and p53 occur at a high frequency in human CRC, including the activation of oncogenic Ras, loss of function of APC, and dominant negative mutations in p53. This potentially implicates dysregulation of the Ras-MAPK, Wnt, and DNA repair pathways associated with the products of these respective genes. Prior studies in patients have revealed two or more of these pathways to be dysfunctional in the majority of clinical cases, suggesting a greater need for multigenic models of CRC. To better understand tumorigenesis in the context of different genetic alterations, we have developed Drosophila melanogaster models of CRC by mispressing them individually (one-hit), in pairs (two-hit), and collectively (three-hit). Using these models, we will investigate the interactions among the aforementioned molecular pathways, characterizing the expression of pathway-specific downstream target genes, changes in the cell cycle, and tumor progression. To generate tumors in the Drosophila intestine, we misexpressed the genes under study using escargot-GAL4 (esg-GAL4), which specifically drives the expression of tumor-promoting genes in intestinal stem cells, in tandem with the heat shock-inducible FLP-FRT system. We quantified the survival rates of mutant and control flies to determine the impact of these mutations on survival. Additionally, the phenotypes and gene expression patterns of intestinal tumor cells were analyzed and compared via dissection of third-instar larvae and subsequent use of immunohistochemistry. Here, we present our preliminary data from these experiments and our progress in developing a preclinical model of CRC in Drosophila.

    Publication Date

    4-17-2024

    Project Designation

    Independent Research

    Primary Advisor

    Madhuri Kango-Singh

    Primary Advisor's Department

    Biology

    Keywords

    Stander Symposium, College of Arts and Sciences

    Institutional Learning Goals

    Scholarship; Practical Wisdom; Critical Evaluation of Our Times

    Establishing Drosophila Intestinal Tumor Models to Study Signaling Interactions that Regulate Tumor Growth

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