Estradiol increases ER-negative breast cancer metastasis in an experimental model.

Estradiol increases ER-negative breast cancer metastasis in an experimental model.
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DOI:
10.1007/s10585-012-9559-0
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发表时间:
2013-08
影响因子:
4
通讯作者:
Helferich, William G.
Helferich, William G.
中科院分区:
医学3区
文献类型:
--
作者:
Yang, Xujuan;Belosay, Aashvini;Du, Mengyuan;Fan, Timothy M.;Turner, Russell T.;Iwaniec, Urszula T.;Helferich, William G.

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乳腺癌(BC)是影响美国女性的最常见癌症,转移性乳腺癌是导致死亡的主要原因。雌二醇在ER阳性BC中所起的作用已得到充分证实,但它对ER阴性BC的作用方式仍不清楚。在本研究中,我们利用了一个实验模型的BC转移到肺内的ER阴性小鼠4T1细胞注射到小鼠通过侧尾静脉。在注射5 × 103个细胞后观察到56%的转移发生率,因此选择该细胞数量来研究雌二醇对ER阴性BC转移的潜在刺激作用。将切除卵巢的雌性小鼠随机分为雌二醇组和对照组,每组16只小鼠,雌二醇组皮下植入雌二醇颗粒。结果表明,雌二醇加速BC转移所示的生物发光成像。此外,雌二醇增强了转移性肿瘤集落的形成,并增加了肺中肿瘤结节的大小,这部分是由于转移性肿瘤中增殖细胞的增加。在体外,雌二醇增加4T1细胞的运动性和侵袭性,并且对细胞运动性的刺激作用不被ICI 182,780阻断,证实ER不参与该过程。本研究的结果表明,雌二醇在整个动物的ER阴性BC转移中发挥作用。
Breast cancer (BC) is the most common cancer affecting women in the United States and metastatic breast cancer is the leading cause of death. The role estradiol plays in ER-positive BC is well-documented, but the way it contributes to ER-negative BC remains unclear. In the present study, we utilized an experimental model of BC metastasis into lung by injecting ER-negative murine 4T1 cells into mice via the lateral tail vein. A 56 % metastasis occurrence rate following the injection of 5 × 103 cells was observed, thus this cell number was selected to study the potential stimulatory effect of estradiol on ER-negative BC metastasis. Female ovariectomized mice were randomized into estradiol and control groups with 16 mice per group, and estradiol pellets were implanted subcutaneously in the estradiol group. Results demonstrated that estradiol accelerated BC metastasis as indicated by bioluminescent imaging. In addition, estradiol enhanced metastatic tumor colony formation and increased the size of tumor nodules in the lungs, which were due, in part, to the increase in proliferative cells in the metastatic tumors. In vitro, estradiol increased the motility and invasion of 4T1 cells, and the stimulatory effect on cell motility was not blocked by ICI 182, 780, confirming that ER was not involved in the process. Results from the present study suggest that estradiol plays a role in ER-negative BC metastasis in whole animals.
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