Establishing Drosophila Intestinal Tumor Models to Study Signaling interactions that regulate tumor growth
Ayesha Sheikh, Michael Gruhot, Anthony Latronica, Sydney Anderson, Arushi Rai; other authors: Amit Singh, Madhuri Kango-Singh
In 2023, the American Cancer Society estimated 106,970 new cases of colon cancer and about 50000 new cases of rectal cancer in the USA. Colorectal Cancer (CRC) is the second most lethal cancer. Studies in patients revealed the genetic lesions associated with CRC. These include activation of oncogenic Ras, loss of function of APC, and dominant negative p53 mutations. Genetic mutations in these three genes- RAS, APC and p53 have a high incidence rate in human CRC. We have developed a Drosophila melanogaster CRC model by integrating all three mutations in a single fly line. To understand the expression of each mutated gene on tumorigenesis, ‘one-’, ‘two-’, and ‘three-hit’ models were also made. Using these models we plan to establish how combinations of genetic alterations promote intestinal tumor growth. We will investigate the interactions between the molecular pathways involved by assessing the effects on the expression of pathway-specific target genes in the tumors and characterizing tumor progression in our CRC models.To generate CRC tumors in the Drosophila intestine, we misexpressed the genes under study using Esc-GAL4, which will drive the expression of tumor-promoting genes specifically in intestinal stem cells. We quantified the survival rates of mutant and control flies to determine the impact of these genetic alterations on survival. Second, by dissecting the gut of third-instar larvae we assessed the phenotypes of intestinal tumors. We have preliminary data from our immunohistochemistry studies that will be compared between all CRC models. Here, we present our progress on the development and assessment of CRC models using the power of Drosophila.
Madhuri Kango-Singh, Amit Singh
Primary Advisor's Department
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" (2023). Stander Symposium Projects. 3244.