Expression of selected Aurora A kinase substrates in solely estrogen-induced ectopic uterine stem cell tumors in the Syrian hamster kidney.
Expression of selected Aurora A kinase substrates in solely estrogen-induced ectopic uterine stem cell tumors in the Syrian hamster kidney.
复制标题
选定的 Aurora A 激酶底物在仅雌激素诱导的叙利亚仓鼠肾脏异位子宫干细胞肿瘤中的表达。
DOI：
10.1007/978-0-387-69080-3_39
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发表时间：
2008
影响因子：
--
通讯作者：
Li,JonathanJ
中科院分区：
文献类型：
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作者：
Hontz,AdrianneE;Li,SaraA;Salisbury,JeffreyL;Lingle,WilmaL;Li,JonathanJ
Aurora A (AurA) 的持续过度表达、中心体扩增、染色体不稳定和非整倍性是人类乳腺癌前阶段和原发性导管乳腺癌 (BC) 以及动物模型中 17β-雌二醇 (E2) 诱导的肿瘤发生中高频发生的显着特征。我们报道，与胆固醇处理的对照肾脏相比，在原发性 E2 诱导的雄性叙利亚仓鼠子宫干细胞样肾肿瘤 (EUTK) 中，AurA/B 蛋白表达分别增加 8.7 倍和 4.6 倍。与持续暴露于 E2 的动物的肿瘤相比，停药 10 天或同时服用柠檬酸他莫昔芬后，原发性肿瘤中的 AurA/B 蛋白表达分别减少了 78-79% 和 81-64%。这些数据表明 AurA/B 表达受到雌激素通过雌激素受体 a 的调节。为了确定 E2 诱导的 Aur 激酶过度表达是否可能通过特定底物的磷酸化导致肿瘤发生过程中观察到的变化，我们分析了组蛋白 H3 和 Xklp2 (TPX2) 靶向蛋白的蛋白表达。与胆固醇处理的对照肾脏样本相比，在 E2 诱导的肿瘤中，组蛋白 H3 和 TPX2 分别显着过度表达 3.7 倍和 1.6 倍。免疫组织化学显示TPX2蛋白表达基本上局限于肿瘤灶细胞。总的来说，这些数据表明 AurA/B 的过度表达受到雌激素的控制，并且 Aur 激酶蛋白底物的失调与引发在肿瘤发生过程中观察到的变化有关。
Sustained over-expression of Aurora A (AurA), centrosome amplification, chromosomal instability, and aneuploidy are salient features that occur in high frequency in human breast premalignant stages and in primary ductal breast cancer (BC), as well as in 17β-estradiol (E2)-induced oncogenesis in animal models. We have reported that AurA/B protein expression increases 8.7-and 4.6-fold, respectively, in primary E2-induced male Syrian hamster uterine stem cell-like tumors of the kidney (EUTK) when compared with cholesterol-treated control kidneys. Upon a 10-day E2-withdrawal or coadministration of tamoxifen citrate, a 78–79% and 81–64% reduction in AurA/B protein expression, respectively, were observed in primary tumors when compared with tumors from animals continuously exposed to E2. These data indicate that AurA/B expression is regulated by estrogens via estrogen receptor a. To determine whether this E2-induced over-expression of the Aur kinases may contribute to the alterations observed during oncogenesis via their phosphorylation of specific substrates, we analyzed the protein expression of histone H3 and targeting protein for Xklp2 (TPX2). Histone H3 and TPX2 were significantly over-expressed 3.7- and 1.6-fold, respectively, in E2-induced tumors when compared with cholesterol-treated control kidney samples. Immunohistochemistry revealed that TPX2 protein expression was essentially confined to tumor foci cells. Collectively, these data indicate that over-expression of AurA/B is under estrogen control and that the deregulation of Aur kinase protein substrates is implicated in eliciting the alterations observed during oncogenesis.