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Epithelial oestrogen receptor α is dispensable for the development of oestrogen‐induced cervical neoplastic diseases
Author(s) -
Son Jieun,
Park Yuri,
Chung SangHyuk
Publication year - 2018
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5069
Subject(s) - stromal cell , stroma , cancer research , biology , epithelium , progesterone receptor , cervical intraepithelial neoplasia , cervical cancer , estrogen receptor , pathology , medicine , cancer , immunology , immunohistochemistry , breast cancer
Human papillomavirus (HPV) is required but not sufficient for cervical carcinoma (CxCa) development. Oestradiol (E 2 ) promotes CxCa development in K14E7 transgenic mice expressing the HPV16 E7 oncoprotein under the control of the keratin (K14) promoter. E 2 mainly functions through oestrogen receptor α (ERα). However, the role of ERα in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERα‐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 E 2 induced cervical epithelial cell proliferation in epithelial ERα‐deficient mice. We also found that E 2 promoted the development of CIN and CxCa in epithelial ERα‐deficient K14E7 mice and that all neoplastic epithelial cells were negative for ERα. In addition, proliferation indices were similar between ERα – and ERα + CxCa. These results indicate that epithelial ERα is not necessary for E 2 ‐induced CIN and CxCa. Taking these findings together, we conclude that stromal ERα rather than epithelial ERα mediates oncogenic E 2 signalling in CxCa. Our results support stromal ERα signalling as a therapeutic target for the disease. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.