Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression.
Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression.
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DOI：
10.1038/cddis.2014.224
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发表时间：
2014-05-22
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
雌激素受体-α阳性（ER+）乳腺癌占人类乳腺癌的大多数，但这种亚型乳腺癌的分子机制仍然知之甚少。在这里，我们发现Tip 30 −/−MMTV-Neu小鼠中出现的ER+乳腺腔肿瘤表现出腔祖细胞基因特征的富集增加。在雌性Balb/c小鼠中，Tip 30基因的缺失增加了乳腺干细胞和祖细胞群的比例，并增加了对ER+乳腺腔肿瘤的易感性。此外，Tip 30 −/−管腔祖细胞显示出分化为成熟ER+管腔细胞和FoxA 1表达的倾向增加。通过FoxA 1特异性的shRNA敲低Tip 30 −/−祖细胞中FoxA 1的表达，减少了它们向ER+成熟管腔细胞的分化。综上所述，我们的结果表明，TIP 30是维持乳腺腔谱系中ER+和ER−管腔池的关键调节因子，其缺失促进ER+管腔祖细胞和成熟细胞的扩增以及ER+乳腺肿瘤发生。
Estrogen receptor-alpha positive (ER+) breast cancers comprise the majority of human breast cancers, but molecular mechanisms underlying this subtype of breast cancers remain poorly understood. Here, we show that ER+ mammary luminal tumors arising in Tip30−/−MMTV-Neu mice exhibited increased enrichment of luminal progenitor gene signature. Deletion of the Tip30 gene increased proportion of mammary stem and progenitor cell populations, and raised susceptibility to ER+ mammary luminal tumors in female Balb/c mice. Moreover, Tip30−/− luminal progenitors displayed increases in propensity to differentiate to mature ER+ luminal cells and FoxA1 expression. Knockdown of FoxA1 expression in Tip30−/− progenitors by shRNA specific for FoxA1 reduced their differentiation toward ER+ mature luminal cells. Taken together, our results suggest that TIP30 is a key regulator for maintaining ER+ and ER−luminal pools in the mammary luminal lineage, and loss of it promotes expansion of ER+ luminal progenitors and mature cells and ER+ mammary tumorigenesis.
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DOI：
10.1073/pnas.0912708107
发表时间：
2010-04-13
影响因子：
11.1
作者：
Gatza, Michael L.;Lucas, Joseph E.;Nevins, Joseph R.
通讯作者：
Nevins, Joseph R.
DOI：
10.1073/pnas.0400699101
发表时间：
2004-03-23
影响因子：
11.1
作者：
Liu, BY;McDermott, SP;Alexander, CM
通讯作者：
Alexander, CM
DOI：
10.1073/pnas.0807640106
发表时间：
2009-03-24
影响因子：
11.1
作者：
Li, Wenjing;Ferguson, Brian J.;Watson, Christine J.
通讯作者：
Watson, Christine J.
影响因子：
7.4
作者：
Allred, DC;Brown, P;Medina, D
通讯作者：
Medina, D
DOI：
10.1073/pnas.0711613105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Liu, Suling;Ginestier, Christophe;Wicha, Max S.
通讯作者：
Wicha, Max S.