FoxM1（Forkhead box protein M1）是一個(gè)癌蛋白,在乳腺癌中,，F(xiàn)oxM1高表達(dá)總是與較差的愈后和細(xì)胞分化不完全有關(guān),。但FoxM1是如何調(diào)節(jié)乳腺細(xì)胞分化的目前尚不清楚。
本文的研究者發(fā)現(xiàn),，F(xiàn)oxM1以轉(zhuǎn)錄抑制因子的身份，來調(diào)節(jié)管腔上皮祖細(xì)胞分化的。在乳腺再生的過程中高表達(dá)FoxM1會(huì)導(dǎo)致管腔上皮祖細(xì)胞數(shù)量增多和乳腺導(dǎo)管形態(tài)紊亂,。與之相反，敲減FoxM1則會(huì)導(dǎo)致乳腺細(xì)胞的過度分化,。研究表明,，F(xiàn)oxM1是通過促進(jìn)GATA3啟動(dòng)子區(qū)甲基化,，從而抑制GATA-3轉(zhuǎn)錄來達(dá)到這一效果的。而GATA-3是一個(gè)轉(zhuǎn)錄因子,，其作用正是維持乳腺細(xì)胞的導(dǎo)管分化,。
這一研究成果說明了FoxM1是調(diào)節(jié)乳腺細(xì)胞分化的關(guān)鍵因子，并為乳腺癌的治療提供了一個(gè)好的靶標(biāo),。（生物谷 Bioon.com ）
doi:10.1016/j.celrep.2012.05.005
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FoxM1 Regulates Mammary Luminal Cell Fate
Janai R. Carr, Megan M. Kiefer, Hyun Jung Park, Jing Li, Zebin Wang, Joel Fontanarosa, Danielle DeWaal, Dragana Kopanja, Elizaveta V. Benevolenskaya, Grace Guzman, Pradip Raychaudhuri
Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.
