P53 Mutation Induces Epithelial-to-Mesenchymal Transition (EMT) Associated with Stem Cell Properties and Tumorigenesis in Fallopian Tube Cells

<b>Background/Objectives</b>: Type II ovarian cancer, including high-grade serous carcinoma (HGSC), is genetically unstable and exhibits frequent mutations in the tumor suppressor genes. Mutations of <i>TP53</i> and <i>BRCA1</i> genes have been associated with HGSC, which has been suggested as a subtype that arises from the fallopian tube lesion called serous tubal intraepithelial carcinoma (STIC). Although <i>TP53</i> and <i>BRCA1</i> genes are well-known tumor suppressor genes, the actual effects of <i>TP53</i> and <i>BRCA1</i> mutations in enhancing the development of ovarian cancer initiated from STIC are poorly understood. <b>Methods:</b> In this study, we knocked out <i>Trp53</i> and <i>Brca-1</i> in epithelial cell clones derived from mice fallopian tube tissues (known as oviducts) and investigated the potential involvement of these two mutations in inducing cancer stem-like cells as cancer-initiating cells. <b>Results:</b> We have shown that the knockout of <i>Trp53</i> induced oviduct cells to undergo EMT and acquire stem cell characteristics. <b>Conclusions:</b><i>Trp53</i> mutation may induce the early stage of precursor lesions formation at the distal end of the oviducts.