Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists
Prevention and treatment of cervical cancer in mice using estrogen receptor antagonists
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DOI：
10.1073/pnas.0911436106
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发表时间：
2009-11-17
影响因子：
11.1
通讯作者：
Lambert, Paul F.
中科院分区：
文献类型：
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作者：
Chung, Sang-Hyuk;Lambert, Paul F.
大多数人类宫颈癌与高危人乳头瘤病毒 (HPV) 类型有关。在 HPV 相关癌症的小鼠模型中，雌激素是宫颈癌和阴道癌发展所必需的。小鼠中这些癌症的发生也需要雌激素受体α（ERα）。这些数据与对女性的观察结果一致，即长期使用口服避孕药或多胎妊娠会显着增加 HPV 阳性女性患宫颈癌的风险。在本研究中，我们检查了干扰 ER α 功能的药物是否能有效治疗和/或预防小鼠宫颈癌。我们提供的证据表明，完全 ER 拮抗剂 ICI 182,780 (ICI) 以及选择性 ER 调节剂雷洛昔芬可有效清除宫颈和阴道的癌症及其前驱病变。此外，ICI 能够预防患有先兆病变的小鼠患癌症。这些发现表明 ER 拮抗剂在控制女性下生殖道妇科疾病方面具有潜在价值。
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 (ER alpha) 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 ER alpha 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.