@article {1634916,
	title = {Oncogenic Events Dictate the Types and Locations of Gynecological Malignancies Originating from  Mesothelial and M{\"u}llerian-Derived Epithelial Cells},
	journal = {Cancers (Basel)},
	volume = {14},
	number = {3},
	year = {2022},
	month = {2022 Feb 08},
	abstract = {Ovarian and uterine cancers are the most prevalent types of gynecological malignancies originating from mesothelial and/or M{\"u}llerian-derived epithelial cells. Recent genomic studies have identified common mutations in them that affect signaling pathways such as p53, PTEN/PI3K, RAS, and WNT pathways. However, how these mutations and their corresponding deregulated pathways affect gynecological cancer development from their cells-of-origin remains largely elusive. To address this, we performed the intrabursal injection of Cre-expressing adenovirus under the control of Krt8 promoter (Ad-K8-Cre) to mice carrying combinations of various conditional alleles for cancer genes. We found that Ad-K8-Cre specifically targeted mesothelial cells, including ovarian surface epithelial (OSE) cells (mainly the LGR5+ subset of OSE cells) and mesothelial cells lining the fallopian tube (FT) serosa; the injected Ad-K8-Cre also targeted M{\"u}llerian-derived epithelial cells, including FT epithelial cells and uterine endometrial epithelial cells. The loss of p53 may preferentially affect M{\"u}llerian-derived epithelial cells, leading to the development of uterine and ovarian malignancies, whereas PTEN-loss may preferentially affect mesothelial cells, leading to the development of ovarian endometrioid malignancies (upon KRAS-activation or APC-loss) or adenoma on the FT surface (upon DICER-loss). Overall, our data suggest that different Krt8+ mesothelial and epithelial cell types in the female reproductive system may have different sensitivities toward oncogenic mutations and, as a result, oncogenic events may dominantly determine the locations and types of the gynecological malignancies developed from them.},
	issn = {2072-6694},
	doi = {10.3390/cancers14030841},
	author = {Park, Eun-Sil and Xiang, Dongxi and Xie, Ying and Bronson, Roderick T. and Li, Zhe}
}
