Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model
Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model
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DOI：
10.1073/pnas.0409883102
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发表时间：
2005-02-15
影响因子：
11.1
通讯作者：
Lambert, PF
中科院分区：
文献类型：
--
作者：
Brake, T;Lambert, PF
宫颈癌是全世界妇女癌症死亡的主要原因。高危人乳头瘤病毒（HPV）是宫颈癌的主要病因，但其他因素可能导致宫颈癌，因为这些癌症通常在初次接触HPV后数十年发生。雌激素被认为是这样的辅因子之一;然而，其在人类宫颈癌中的时间要求尚不清楚。在这里，我们评估的时间要求雌激素在宫颈癌的HPV相关的宫颈癌小鼠模型。与雌激素治疗6个月后的肿瘤相比，用雌激素治疗9个月的HPV 16转基因小鼠中产生的肿瘤的大小大大增加。HPV 16转基因小鼠用雌激素治疗6个月，然后3个月没有外源性雌激素，肿瘤明显较少，肿瘤较小，侵袭性较低，比那些在小鼠治疗了整整9个月。重要的是，与用雌激素治疗6个月的小鼠相比，用雌激素治疗9个月的前6个月的小鼠中出现的宫颈癌必须消退，这是基于这些小鼠中癌症的发病率降低，然后立即进行分析。我们的结论是雌激素不仅在宫颈癌的发生中起着关键作用，而且在这种小鼠模型中的持续性和持续发展中也起着关键作用。这些发现提高了临床相关的可能性，如果人类宫颈癌有一个类似的依赖雌激素的持续肿瘤生长，那么抗雌激素治疗可能是有效的治疗宫颈癌。
Cervical cancer is a leading cause of death by cancer among women worldwide. High-risk human papillomaviruses (HPVs) are the major etiological agents for cervical cancer, but other factors likely contribute to cervical cancer, because these cancers commonly arise decades after initial exposure to HPV. Estrogen is thought to be one such cofactor; however, its temporal requirements in human cervical cancer are not known. Here we evaluate the temporal requirements of estrogen in cervical carcinogenesis in a mouse model for HPV-associated cervical cancer. Tumors arising in HPV16 transgenic mice treated with estrogen for 9 months were greatly increased in their size compared with tumors developing after 6 months of estrogen treatment. HPV16 transgenic mice treated 6 months with estrogen followed by 3 months without exogenous estrogen had significantly fewer tumors and the tumors were smaller and less aggressive than those arising in mice treated the full 9 months. Importantly, cervical cancers that arose in the mice treated the first 6 of 9 months with estrogen must have regressed, based upon the reduced incidence of cancers in these mice compared with those treated for 6 months with estrogen, then immediately analyzed. We conclude that estrogen plays a critical role not only in the genesis of cervical cancer but also in its persistence and continued development in this mouse model. These findings raise the clinically relevant possibility that, if human cervical cancer has a similar dependence on estrogen for continued tumor growth, then antiestrogen therapy may be effective in the treatment of cervical cancer.