Wnt signaling can substitute for estrogen to induce division of ERalpha-positive cells in a mouse mammary tumor model.

Wnt signaling can substitute for estrogen to induce division of ERalpha-positive cells in a mouse mammary tumor model.
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DOI:
10.1016/j.canlet.2009.07.012
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发表时间:
2010-03-01
期刊:
影响因子:
9.7
通讯作者:
Alexander, Caroline M.
Alexander, Caroline M.
中科院分区:
医学1区
文献类型:
--
作者:
Mastroianni, Melissa;Kim, Soyoung;Kim, Young Chul;Esch, Amanda;Wagner, Caroline;Alexander, Caroline M.

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雌激素与雌激素受体(ER,主要是ERα)的相互作用诱导人乳腺肿瘤细胞的生长。相比之下,ERα阳性细胞被描述为正常乳腺中的非分裂细胞(尽管雌激素对ERα细胞的刺激会指导邻近细胞的分裂)。然而,在正常乳腺组织中有一小部分细胞亚群是ERα阳性的,可以分裂,因此与人乳腺肿瘤细胞具有相同的特性。为了研究它们的生长调节模式,我们测量了正常生长期间分裂的ERα+细胞的比例,并将其与致癌Wnt效应物刺激的腺体进行比较。首先,我们发现ERα+细胞和ERα−细胞的分裂速率没有差异,无论细胞群对雌激素还是Wnt有丝分裂原有反应。分裂的ERα+乳腺上皮细胞的比例在妊娠反应中增加(10倍),在异位Wnt信号传导反应中观察到类似的增加。我们认为Wnt信号可以取代雌激素来驱动总人口增长(包括ERα+细胞)。尽管E-ERα衍生的促有丝分裂反应位于少数管腔细胞中,Wnt-LRP 5/6衍生的促有丝分裂反应位于少数基底细胞中,但总体而言,乳腺上皮细胞群的生长反应非常相似。
The interaction of estrogen with the estrogen receptor (ER, principally ERα) induces growth of human breast tumor cells. In contrast, ERα-positive cells have been described as non-dividing cells in normal breast (though estrogen stimulation of ERα cells directs the division of neighboring cells). However, there is a small sub-population of cells in normal mammary tissue that are ERα-positive, that can divide, and therefore share this property with human breast tumor cells. In order to investigate their pattern of growth regulation, we measured the fraction of dividing ERα+ cells during normal growth and compared that to glands stimulated by oncogenic Wnt effectors. First, we found there was no difference between the rate of division of ERα+ cells and ERα− cells, whether the population was responding to estrogen or Wnt mitogens. The proportion of dividing ERα+ mammary epithelial cells was increased (10×) in response to pregnancy, and similar increases were observed in response to ectopic Wnt signaling. We propose that Wnt signaling can substitute for estrogen to drive total population growth (that includes ERα+ cells). Although the E-ERα-derived mitogenic response is situated in a minority of the luminal cells, and the Wnt-LRP5/6 –derived mitogenic response is situated in a minority of basal cells, overall, the growth response of the mammary epithelial population is remarkably similar.
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