乳腺癌腫瘤干細(xì)胞在乳腺癌疾病的擴(kuò)散與進(jìn)展方面起著關(guān)鍵作用,。近期，美德州大學(xué)MD安德森癌癥中心的科學(xué)家認(rèn)為，對活躍的p53基因?yàn)楣羧橄倌[瘤干細(xì)胞提供了潛在路徑。
長期以來,，研究者認(rèn)為p53基因可控制DNA損傷、缺陷的細(xì)胞自我凋亡,，并能激活RNA,。這能防止分布在器官上的上皮分化細(xì)胞，轉(zhuǎn)化為類似于間充質(zhì)干細(xì)胞-受TGF-B(beta)刺激的細(xì)胞,。
間充質(zhì)細(xì)胞是移動(dòng)的成體干細(xì)胞,，能自我繁殖，并分化為各種細(xì)胞類型,。MD安德森癌癥中心分子細(xì)胞腫瘤系的教授談到：防止上皮細(xì)胞向間充質(zhì)細(xì)胞轉(zhuǎn)化在癌癥轉(zhuǎn)移方面發(fā)揮了重要作用,。
癌癥治療的希望
我們發(fā)現(xiàn)p53激活micro RNA miR-200c，使具有干細(xì)胞特性的細(xì)胞恢復(fù)到上皮細(xì)胞的形式,。這一方法可對具有干細(xì)胞特性的腫瘤起始細(xì)胞產(chǎn)生治療功能,。
研究表發(fā)大約80%的各類實(shí)體瘤開始于上皮細(xì)胞。然而,，90%的癌癥死亡率源于癌癥轉(zhuǎn)移并擴(kuò)散到身體的其他器官,。
上皮細(xì)胞間質(zhì)轉(zhuǎn)型（EMT）及其逆向過程在胚胎發(fā)展過程中發(fā)揮重要作用,。研究者將EMT激活與癌癥的發(fā)展與轉(zhuǎn)移相聯(lián)系。最近的研究將EMT與在正常和轉(zhuǎn)化細(xì)胞中干細(xì)胞特性的獲取相聯(lián)系,。
細(xì)胞狀態(tài)依賴于p53, miR-200c 水平。
一系列的實(shí)驗(yàn)表明p53蛋白質(zhì)激活miR-200c,，產(chǎn)生microRNA,，蛋白質(zhì)和miR-200c的表達(dá)上下起伏。
P53基因突變發(fā)生在一半以上的腫瘤上,，p53基因的失活與癌癥相關(guān)類型中的糟糕的病癥相關(guān),。通過miR-200c的重新表達(dá)，恢復(fù)p53基因突變喪失的功能可能是治療p53缺陷腫瘤不錯(cuò)的治療方案,。該研究發(fā)表于Nature Cell Biology雜志上,。（生物谷Bioon.com）
英文鏈接：http://www.sciencedaily.com/releases/2011/02/110225164707.htm
中文鏈接：http://www.chinastemcell.org/page/zixun_xwdtlist.aspx?infoid=996
生物谷推薦英文摘要
Nature Cell Biology (2011) doi:10.1038/ncb2173
p53 regulates epithelial–mesenchymal transition and stem cell properties through modulating miRNAs
Chun-Ju Chang, Chi-Hong Chao, Weiya Xia, Jer-Yen Yang, Yan Xiong, Chia-Wei Li, Wen-Hsuan Yu, Sumaiyah K. Rehman, Jennifer L. Hsu,Heng-Huan Lee,Mo Liu,Chun-Te Chen,Dihua Yu& Mien-Chie Hung
The epithelial–mesenchymal transition (EMT) has recently been linked to stem cell phenotype1, 2. However, the molecular mechanism underlying EMT and regulation of stemness remains elusive. Here, using genomic approaches, we show that tumour suppressor p53 has a role in regulating both EMT and EMT-associated stem cell properties through transcriptional activation of the microRNA miR-200c. p53 transactivates miR-200c through direct binding to the miR-200c promoter. Loss of p53 in mammary epithelial cells leads to decreased expression of miR-200c and activates the EMT programme, accompanied by an increased mammary stem cell population. Re-expressing miR-200c suppresses genes that mediate EMT and stemness properties3, 4 and thereby reverts the mesenchymal and stem-cell-like phenotype caused by loss of p53 to a differentiated epithelial cell phenotype. Furthermore, loss of p53 correlates with a decrease in the level of miR-200c, but an increase in the expression of EMT and stemness markers, and development of a high tumour grade in a cohort of breast tumours. This study elucidates a role for p53 in regulating EMT–MET (mesenchymal–epithelial transition) and stemness or differentiation plasticity, and reveals a potential therapeutic implication to suppress EMT-associated cancer stem cells through activation of the p53–miR-200c pathway.
