Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists.
The majority of human cervical cancers are associated with the high-risk human papillomavirus (HPV) types. In mouse models for HPV-associated cancers, estrogen is required for the development of cervical and vaginal cancers. The estrogen receptor alpha (ERalpha) also is required in mice for these cancers to arise. These data are consistent with the observation in women that long-term use of oral contraceptives or multiple pregnancies significantly increases the risk for cervical cancer in HPV-positive women. In the present study, we examined whether drugs that interfere with the function of ERalpha are effective in treating and/or preventing cervical cancer in mice. We provide evidence that a complete ER antagonist, ICI 182,780 (ICI), as well as a selective ER modulator, raloxifene, efficiently clear cancer and its precursor lesions in both the cervix and the vagina. Furthermore, ICI was capable of preventing the onset of cancers in mice bearing precursor lesions. These findings point to the potential value of ER antagonists in controlling gynecological disease in the lower reproductive tracts in women.
Chung
Sang-Hyuk
SH
McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Lambert
Paul F
PF
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D030361:Papillomavirus Infections / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D000077267:Fulvestrant; D020849:Raloxifene Hydrochloride; D004958:Estradiol