| First Author | Son J | Year | 2018 |
| Journal | J Pathol | Volume | 245 |
| Issue | 2 | Pages | 147-152 |
| PubMed ID | 29532467 | Mgi Jnum | J:265845 |
| Mgi Id | MGI:6199760 | Doi | 10.1002/path.5069 |
| Citation | Son J, et al. (2018) Epithelial oestrogen receptor alpha is dispensable for the development of oestrogen-induced cervical neoplastic diseases. J Pathol 245(2):147-152 |
| abstractText | 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. E2 mainly functions through oestrogen receptor alpha (ERalpha). However, the role of ERalpha in human CxCa has been underappreciated largely because it is not expressed in carcinoma cells. We have shown that deletion of Esr1 (the ERalpha-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 ERalpha-deficient mice. We also found that E2 promoted the development of CIN and CxCa in epithelial ERalpha-deficient K14E7 mice and that all neoplastic epithelial cells were negative for ERalpha. In addition, proliferation indices were similar between ERalpha(-) and ERalpha(+) CxCa. These results indicate that epithelial ERalpha is not necessary for E2 -induced CIN and CxCa. Taking these findings together, we conclude that stromal ERalpha rather than epithelial ERalpha mediates oncogenic E2 signalling in CxCa. Our results support stromal ERalpha signalling as a therapeutic target for the disease. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
