Spontaneous Transformation of Murine Oviductal Epithelial Cells: A Model System to Investigate the Onset of Fallopian-Derived Tumors.

摘要: High-grade serous carcinoma (HGSC) is the most lethal ovarian cancer histotype. The fallopian tube secretory epithelial cells (FTSECs) are a proposed progenitor cell type. Genetically altered FTSECs form tumors in mice; however, spontaneous HGSC model has not been described. Apart from subpopulation of genetically predisposed women, women develop spontaneously, which associated with aging and lifetime ovulations. A murine oviductal line (MOE(LOW)) was developed continuously passaged culture to mimic cellular (MOE(HIGH)). MOE(HIGH) exhibited loss acetylated tubulin consistent an outgrowth culture. proliferated significantly faster than MOE(LOW), produced more 2D foci 3D soft agar colonies as compared MOE(LOW) were xenografted into athymic female nude mice both subcutaneous intraperitoneal compartments. Only grafts formed that negative for cytokeratin, but positive markers, such glycoprotein 1 Pax8. These considered be poorly differentiated carcinoma. differential molecular profiles between determined using RNA-Seq confirmed by protein expression uncover pathways important transformation, like p53 pathway, FOXM1 WNT signaling, splicing. had enhanced c-myc, Cyclin E, p53, reduced p21. also less sensitive cisplatin DMBA, induce lesions typically repaired base-excision repair. tumorogenesis generated starting normal cells. Their transition involved alterations high-grade humans.