Abstract 97: Investigating the potential function and tumor biology of MDM2: a novel biomarker in differentiated thyroid carcinoma

Background: The mouse double minute 2 (MDM2) gene encode the MDM2 protein which is the negative regulatory factor of the p53 protein. MDM2 forms a complex with p53 and its E3 ubiquitin ligase activity plays a role in the degradation of p53. The overexpression of MDM2 is explored in several malignancies like liver cancer, lung cancer, colorectal cancer, esophagogastric cancer, and breast cancer. Here we identified the potential function of MDM2 in the tumor development and formation of Differentiated thyroid carcinoma (DTC): Papillary thyroid carcinoma (PTC) & Follicular Thyroid Carcinoma (FTC). Methods: Real-Time PCR was performed for the gene-expression study of MDM2 using K1 and FTC133 cell lines and in tissue samples (total of 30 samples- 10 PTC, 10 FTC & 10 control tissue). To discover the biological function, Both the cell lines were treated with different concentrations of SAR405837 (MDM2 inhibitor) and performed cell culture experiments such as MTT assay, scratch assay, colony formation assay, and apoptosis assays. We also examined the protein expression of MDM2 in PTC and FTC tissue samples by Immunohistochemistry and observations were further correlated with clinicopathological parameters in DTC patients with a follow-up study. Results: We found that MDM2 expression was elevated in both PTC and FTC tumor tissue samples and in cell lines. Inhibiting MDM2 by SAR405838 showed a positive correlation in cell viability, cell migration, and cell death in both the cell lines which confirms that MDM2 is involved in tumorigenesis and tumor development of thyroid cancer. We found a significant correlation of MDM2 with clinicopathological parameters of PTC and FTC patients. Conclusion: We determined that MDM2 is upregulated in both papillary and follicular thyroid carcinoma. Moreover, our results suggested that the overexpressed MDM2 may potentially serve as a therapeutic target, and its inhibitorSAR405838 can be used as directed therapy selection and may have clinical utility for patients with differentiated thyroid carcinoma.