Requirement for stromal estrogen receptor alpha in cervical neoplasia.

ABSTRACT: The major etiological factor for cervical cancer is the high-risk human papillomavirus (HPV), which encodes E6 and E7 oncogenes. However, HPV is not sufficient, and estrogen has been proposed as an etiological cofactor for the disease. Its requirement has been demonstrated in mouse models for HPV-associated cervical cancer (e.g., K14E7 transgenic mice). Although germline knockout of estrogen receptor alpha (ER?) renders mice resistant to cervical cancer, the cell-type-specific requirement for ER? is not known. In this study, we demonstrate that temporal deletion of stromal ER? induced complete regression of cervical dysplasia in K14E7 mice. Our results strongly support the hypothesis that stromal ER? is necessary for HPV-induced cervical carcinogenesis and implicate paracrine mechanisms involving ER? signaling in the development of estrogen-dependent cervical cancers. This is the first evidence to support the importance of stromal ER? in estrogen-dependent neoplastic disease of the female reproductive tract.

SUBMITTER: Chung SH 

PROVIDER: S-EPMC3541456 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature