Mutant p53 expression in fallopian tube epithelium drives cell migration

摘要: Ovarian cancer is the fifth leading cause of death among US women. Evidence supports hypothesis that high-grade serous ovarian cancers (HGSC) may originate in distal end fallopian tube. Although a heterogeneous disease, 96% HGSC contain mutations p53. In addition, "p53 signature," or overexpression p53 protein (usually associated with mutation), potential precursor lesion tube derived suggesting an essential role for mutation early tumorigenesis. To further clarify p53-mutation dependent effects on cells, murine oviductal epithelial cells (MOE) were stably transfected construct encoding R273H DNA binding domain p53, most common HGSC. Mutation was not sufficient to transform MOE but did significantly increase cell migration. A similar surface epithelium (MOSE), another progenitor cancer, nor change migration tissue specific mutation. Microarray data confirmed expression changes pro-migratory genes p53(R273H) compared parental which could be reversed by suppressing Slug expression. Combining KRAS(G12V) activation caused transformation into sarcomatoid carcinoma when xenografted nude mice. Elucidating will improve understanding at earliest stage transformation. This information can help develop chemopreventative strategies prevent accumulation additional and reverse progression signature" thereby, improving survival rates.