Research Mentor(s): Abdulsalam Soofi
Authors: Zara Bedella, Emily Warden, Vivie Li, Abdul Soofi, PhD
Epithelial ovarian cancer (EOC) is the most common and most lethal type of ovarian cancer, and secretory cells are believed to be the progenitors of EOC. Pax2 & Pax8 positive secretory cells are oviduct epithelial progenitors and can further differentiate to ciliated cell progeny. Pax2 & Pax8 function in the oviduct and are not present in other healthy organs, thus we seek to understand their role in epithelial ovarian cancer origin and progression. It has been indicated that perhaps this cancer originates from epithelial tissue in the oviduct when homeostasis in this area is disrupted and progresses toward the ovary where it begins to proliferate. To investigate this, we generated double & single KO mouse models of Pax2 and Pax8 to analyze their roles in maintaining the integrity of the oviduct cells and whether these transcription factors will provide a new insight into epithelial homeostasis. Mice carrying conditional KO appeared normal with no evidence of abnormalities. However, after tamoxifen administration and specific deletion of Pax2 & Pax8, these mice failed to conceive even eight weeks following the administration. Additionally, we observed progressive phenotypes at later times in the three combinations of protein deletion (Pax2 KO, Pax8 KO, Pax2/Pax8 double KO) for up to one year after tamoxifen administration. This indicates that Pax2 & Pax8 are critical for maintaining the integrity of the oviduct. This research can work towards a better understanding of how the most prevalent form of ovarian cancer originates and persists, and these transcription factors could ultimately serve as biomarkers for diagnostic and treatment measures.