Alcohol Promotes Mammary Tumor Development via the Estrogen Pathway in Estrogen Receptor Alpha-Negative HER2/neu Mice
Alcohol Promotes Mammary Tumor Development via the Estrogen Pathway in Estrogen Receptor Alpha-Negative HER2/neu Mice
复制标题
DOI：
10.1111/j.1530-0277.2011.01654.x
复制
发表时间：
2012-04-01
影响因子：
3.2
通讯作者：
Nunez, Nomeli P.
中科院分区：
文献类型：
--
作者：
Wong, Amy W.;Dunlap, Sarah M.;Nunez, Nomeli P.
背景：饮酒是乳腺癌的一个既定危险因素。然而，酒精影响乳腺癌发展的机制仍然没有得到解决。从绝经前到绝经后阶段的过渡与全身雌激素水平的急剧下降有关。目前尚不清楚是否乳腺癌的风险归因于饮酒是由不同水平的雌激素发现绝经前后的妇女修改。本研究的目的是确定酒精对乳腺肿瘤发展的影响是否依赖于卵巢雌激素的存在。方法：作为乳腺癌模型，我们使用过表达人表皮生长因子受体2的小鼠乳腺肿瘤病毒（MMTV）-neu转基因小鼠，乳腺上皮中的HER 2/neu的表达，导致雌激素受体α（ER α）阴性乳腺肿瘤的发展。这些小鼠的乳腺肿瘤发生过程与HER 2乳腺癌患者相似。将非卵巢切除（NOVX）和卵巢切除（OVX）的MMTV-neu小鼠暴露于饮用水中的0、5和20%乙醇。乳腺癌的发展和进展的影响，酒精对雌激素的可用性和signaling.Results：我们的数据表明，20%的酒精消费促进肿瘤的发展，只有在卵巢激素的存在下，在MMTV-neu小鼠。肿瘤促进与全身雌激素水平增加、芳香化酶（雌激素合成中的限速酶）表达增加以及20%酒精消耗的MMTV-neu小鼠肿瘤中ER α表达增加相关。此外，我们表明，卵巢切除术（去除卵巢和卵巢激素的生产）阻断了20%的酒精对肿瘤development.Conclusions的影响：我们的研究结果支持的概念，酒精消费促进HER 2乳腺癌的发展，通过雌激素信号通路。此外，他们认为酒精对乳腺癌的影响可以通过阻断雌激素信号来预防。
Background: Alcohol consumption is an established risk factor for breast cancer. Yet, the mechanism by which alcohol affects breast cancer development remains unresolved. The transition from the premenopausal to the postmenopausal phase is associated with a drastic reduction in systemic estrogen levels. It is not clear whether the risk of breast cancer attributable to alcohol consumption is modified by the different levels of estrogen found in pre- and postmenopausal women. The objective of this study is to determine whether the effects of alcohol on mammary tumor development are dependent on the presence of ovarian estrogen.Methods: As a model of breast cancer, we used mouse mammary tumor virus (MMTV)-neu transgenic mice that overexpress the human epidermal growth factor receptor 2 (HER2/neu) in the mammary epithelium, resulting in the development of estrogen receptor alpha (ER alpha)-negative mammary tumors. The mammary tumorigenesis process in these mice is similar to that of patients with HER2 breast cancer. Nonovariectomized (NOVX) and ovariectomized (OVX) MMTV-neu mice were exposed to 0, 5, and 20% ethanol in the drinking water. Breast cancer development and progression were determined alongside the effects of alcohol on estrogen availability and signaling.Results: Our data show that 20% alcohol consumption promoted tumor development in MMTV-neu mice only in the presence of ovarian hormones. Tumor promotion was associated with increased systemic estrogen levels, increased expression of aromatase (the rate-limiting enzyme in estrogen synthesis), and increased expression of ERa in the tumors of 20% alcohol-consuming MMTV-neu mice. Additionally, we show that ovariectomy (removal of the ovaries and ovarian hormone production) blocked the effects of 20% alcohol on tumor development.Conclusions: Our results support the notion that alcohol consumption promotes HER2 breast cancer development via the estrogen signaling pathway. Additionally, they suggest that the effects of alcohol on breast cancer may be prevented by blocking estrogen signaling.