A Proposed Mouse Model for Spontaneous High Grade Serous Carcinoma Progression

Despite modern advancements in cancer treatments, high grade serous ovarian carcinoma (HGSC) remains the deadliest gynecological cancer. Currently, the molecular pathway that leads to the formation and progression of HGSC is not well known. The current paradigm for ovarian cancer development involves tumor cell transfer from the fallopian tube to the ovary. A long-term dietary study by our group facilitated investigation of the relationship between obesity, dietary intervention and spontaneous cancer incidence in C3H/HeJ mice. Over the course of the 18-month study, 22 of 200 female mice presented with ovarian tumors and concurrent oviduct anomalies. In addition, 9 more oviduct anomalies were observed. The aim of this study was to examine the role of oviducts in the development of ovarian cancer in C3H/HeJ mice. Based on previous studies, PTEN is commonly found to be inactivated in HGSC, resulting in uncontrolled growth of tumor cells through the AKT pathway. We hypothesized that PTEN inactivation will also be mirrored in the oviducts associated with ovarian cancer presenting mice, suggesting a relationship to HGSC development. To test this hypothesis, histological examination of tissue morphology, Western blotting and immunohistochemistry analysis of PTEN and proteins associated with its function was performed, to begin elucidating this pathway. Furthermore, use of this mouse strain was evaluated as an in vivo model for HGSC. Results showed no statistical significance between tumor incidence and specific dietary groups. Western analysis showed difference in AKT levels in uterine tubes and ovaries. Histological analysis showed disorganized growth consistent with poorly differentiated ovarian cancer. This encourages new opportunities for study of CH3/HeJ mice as a potential mouse model for naturally occurring ovarian cancer, and for other potential molecular pathways.