Requirement for stromal estrogen receptor alpha in cervical neoplasia.
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 (ERα) renders mice resistant to cervical cancer, the cell-type-specific requirement for ERα is not known. In this study, we demonstrate that temporal deletion of stromal ERα induced complete regression of cervical dysplasia in K14E7 mice. Our results strongly support the hypothesis that stromal ERα is necessary for HPV-induced cervical carcinogenesis and implicate paracrine mechanisms involving ERα signaling in the development of estrogen-dependent cervical cancers. This is the first evidence to support the importance of stromal ERα in estrogen-dependent neoplastic disease of the female reproductive tract.
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Ave, Madison, WI 53706, USA.
Sang-Hyuk
SH
Chung
Myeong Kyun
MK
Shin
Kenneth S
KS
Korach
Paul F
PF
Lambert
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D013629:Tamoxifen / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D013629:Tamoxifen