Development of Low-Grade Serous Ovarian Carcinoma from Benign Ovarian Serous Cystadenoma Cells.

Despite the knowledge about numerous genetic mutations essential for the progression of low-grade serous ovarian carcinoma (LGSOC), the specific combination of mutations required remains unclear. Here, we aimed to recognize the oncogenic mutations responsible for the stepwise development of LGSOC using immortalized HOVs-cyst-1 cells, developed from ovarian serous cystadenoma cells, and immortalized via , , and gene transfection. Furthermore, oncogenic mutations, and , were individually and simultaneously introduced in immortalized HOV-cyst-1 cells. Cell functions were subsequently analyzed via in vitro assays. or double mutant HOV-cyst-1 cells exhibited higher cell proliferation and migration capacity than the wild-type cells, or those with either a or a mutation, indicating that these mutations play a causative role in LGSOC tumorigenesis. Moreover, and double mutants gained tumorigenic potential in nude mice, whereas the cells with a single mutant exhibited no signs of tumorigenicity. Furthermore, the transformation of HOV-cyst-1 cells with and mutants resulted in the development of tumors that were grossly and histologically similar to human LGSOCs. These findings suggest that simultaneous activation of the KRAS/ERK and PIK3CA/AKT signaling pathways is essential for LGSOC development.