Shreya Mishra
Pronouns: she/her/hers
Research Mentor(s): Li-Jyun Syu
Co-Presenter:
Research Mentor School/College/Department: Dermatology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 2 – 11am – 11:50am
Room: League Ballroom
Authors: Shreya Mishra , Dawn Wilbert , Monique Verhaegan, Thomas Saunders , Andrzej Dlugosz, Li-Jyun Syu
Presenter: 78
Abstract
Merkel Cell Polyomavirus (MCPyV) is a human viral pathogen. MCPyV integration into DNA of human cells is linked to Merkel Cell Carcinoma (MCC), a rare and aggressive skin cancer. MCPyV produces two major cancer-associated proteins, large tumor antigen (LTAg) and small tumor antigen (sTAg), and both are found in MCC tumor cells. sTAg is a potent oncogene whereas LTAg blocks the function of a tumor suppressor called RB1, but LTAg may also be involved in regulating cell differentiation, Intriguingly, several different truncated forms of LTAg have been found in different human MCCs, but their role in MCC tumorigenesis is not fully understood. We tested the response of epidermal skin cells to either sTAg alone or sTAG+tLT-Ag339, the longest LTAg reported, in genetically-engineered mouse embryos collected just before birth. Expression of the TAgs was targeted to skin using DNA regulatory elements from the Keratin 5 (K5) gene that is active only in epidermal cells. We examined the structure of 1) control, 2) sTAg, and 3) sTAg+tLTAg339 embryo skin using a tissue stain (H&E), and also measured proliferation (Ki67 protein), and cell-specific protein markers (K5, K8, and Loricrin) using antibody staining. Expression of sTAg alone causes severe abnormalities in epidermis organization, increases proliferation in undifferentiated K5-expressing basal cells, and blocks epidermal differentiation. Mouse embryos expressing sTAg+tLTAg339 have many of the same findings as mice expressing sTAg alone, but they have fewer K5-expressing cells, and appear to activate low-level expression of the MCC-specific protein K8. Out data confirm earlier findings pointing to sTAg as the major oncogene in MCC, and in addition, suggest that the tLTAg339 variant of LTAg may be capable of complementing the activity of sTAg by reprogramming epidermal cells into K8-expressing MCC-like cells.
Biomedical Sciences
