Majd Ajine
Research Mentor: Imad Shureiqi
Mentor Department: Internal Medicine, Medicine
Author(s): Majd Ajine, Imad Shureiqi
Session: Session 1 (9:00 AM – 9:50 AM)
Presentation Type: Poster 11
Abstract
Oncogenic mutations in the KRAS, specifically the G12D, play a central role in colorectal tumorigenesis and cancer progression. In vitro studies showed that the KRASG12D mutation upregulates PPARD expression in intestinal cell lines (PMID: 12036946). PPARD has been also linked to the regulation of chemokines and cytokines; including CCL2 and IL-1B, suggesting that there is a link between oncogenic signaling by KRAS and inflammatory reshaping of the tumor microenvironment. However, although KRASG12D induced PPARD in vitro; its expression in vivo is still up to debate. This project investigates if activation of KRASG12D in intestinal epithelial cells upregulates PPARD expression in vivo and if this upregulation may contribute to changes in chemokine and cytokine signaling. In order to address this. Mouse models expressing KRASG12D under the control of the villin promoter (villin-Cre-ERT-KRASG12D mice) were given tamoxifen by oral gavage to start a change throughout the intestinal epithelium, and villin-Cre-ERT-KRASG12D mice with the gene tdTomato were exposed to 4-hydroxytamoxifen (4-OHT) via enema to localize the activation and tracing. PPARD expression was assessed using qPCR after administering the mice with tamoxifen and 4-OHT. These experiments were aimed to understand whether or not oncogenic KRAS signaling can regulate PPARD expression in vivo, and provide necessary information into a potential mechanism which promotes cancerous signaling pathways in colorectal cancer. Ultimately, this may reveal novel connections between oncogenic signaling and immune microtumors in colorectal tumorigenesis.
