Epithelial oestrogen receptor ? is dispensable for the development of oestrogen-induced cervical neoplastic diseases



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The Journal of Pathology


Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa) development. Oestradiol (E2) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin (K14) promoter. E2mainly functions through oestrogen receptor ? (ER?). However, the role of ER? in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ER??coding gene) in the cervical stroma of K14E7 mice promotes regression of cervical intraepithelial neoplasia (CIN), the precursor lesion of CxCa. Here, we deleted Esr1 in the cervical epithelium but not in the stroma. We found that E2 induced cervical epithelial cell proliferation in epithelial ER??deficient mice. We also found that E2 promoted the development of CIN and CxCa in epithelial ER??deficient K14E7 mice and that all neoplastic epithelial cells were negative for ER?. In addition, proliferation indices were similar between ER?– and ER?+ CxCa. These results indicate that epithelial ER? is not necessary for E2?induced CIN and CxCa. Taking these findings together, we conclude that stromal ER? rather than epithelial ER? mediates oncogenic E2 signalling in CxCa. Our results support stromal ER? signalling as a therapeutic target for the disease.



cervical cancer, ER?, human papillomavirus, HPV, mouse model


Copyright 2018 The Journal of Pathology. This is a post-print version of a published paper that is available at: https://onlinelibrary.wiley.com/doi/full/10.1002/path.5069. Recommended citation: Son, Jieun, Yuri Park, and Sang-Hyuk Chung. "Epithelial oestrogen receptor ? is dispensable for the development of oestrogen?induced cervical neoplastic diseases." The Journal of pathology 245, no. 2 (2018): 147-152. DOI: 10.1002/path.5069. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission.