乳腺癌是由于惡性腫瘤侵略并破壞乳房正常組織而形成的癌變腫瘤，也可能擴(kuò)散到其他地方,，是全世界女性最常見(jiàn)的癌病，世界一年約有50萬(wàn)人死于乳腺癌。美國(guó)研究者對(duì)IGF-1調(diào)控乳腺癌miRNA表達(dá)的機(jī)制進(jìn)行了系統(tǒng)研究*，研究結(jié)果發(fā)表在11月30日的PLoS ONE上,。
MiRNA在腫瘤的發(fā)展和轉(zhuǎn)變中起著重要調(diào)控作用，調(diào)控腫瘤細(xì)胞增殖,，分化和細(xì)胞凋亡,。許多miRNA表達(dá)受信號(hào)分子調(diào)控，如生長(zhǎng)因子和激素分子等,。在乳腺癌中，胰島素樣生長(zhǎng)因子-1（Insulin-like Growth Factor 1,，IGF-1）可作為促細(xì)胞分裂劑,，能通過(guò)調(diào)控MAPK和PI3K/AKT信號(hào)通路，促進(jìn)細(xì)胞增殖和凋亡,，轉(zhuǎn)而促進(jìn)腫瘤的發(fā)生,。
本研究中，研究人員利用miRNA表達(dá)譜芯片找到了一組已知的抑癌和致癌microRNA（miRNA）可由IGF-1信號(hào)因子直接調(diào)控（由聯(lián)川生物提供miRNA芯片檢測(cè)服務(wù)）,。在進(jìn)行IGF-1刺激前,，選擇性地抑制MAPK或AKT通路，可阻止抑癌miRNA的表達(dá),。研究人員首次發(fā)現(xiàn)在雌激素受體陽(yáng)性的MCF-7乳癌細(xì)胞系內(nèi)直接由IGF-1信號(hào)通路調(diào)控的miRNA, 并且證實(shí)了激酶信號(hào)通路可以調(diào)控一小組miRNA的表達(dá),。
本研究給出乳腺癌中IGF-1信號(hào)調(diào)控機(jī)制的新發(fā)現(xiàn)，對(duì)深入了解乳腺癌的發(fā)生,，發(fā)展機(jī)制起著重要作用,。(生物谷Bioon.com)
doi:10.1371/journal.pone.0049067
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Insulin-Like Growth Factor-1 Signaling Regulates miRNA Expression in MCF-7 Breast Cancer Cell Line
Elizabeth C. Martin, Melyssa R. Bratton, Yun Zhu, Lyndsay V. Rhodes, Syreeta L. Tilghman, Bridgette M. Collins-Burow, Matthew E.
In breast carcinomas, increased levels of insulin-like growth factor 1 (IGF-1) can act as a mitogen to augment tumorigenesis through the regulation of MAPK and AKT signaling pathways. Signaling through these two pathways allows IGF-1 to employ mechanisms that favor proliferation and cellular survival. Here we demonstrate a subset of previously described tumor suppressor and oncogenic microRNAs (miRNAs) that are under the direct regulation of IGF-1 signaling. Additionally, we show that the selective inhibition of either the MAPK or AKT pathways prior to IGF-1 stimulation prevents the expression of previously described tumor suppressor miRNAs that are family and cluster specific. Here we have defined, for the first time, specific miRNAs under the direct regulation of IGF-1 signaling in the estrogen receptor positive MCF-7 breast cancer cell line and demonstrate kinase signaling as a modulator of expression for a small subset of microRNAs. Taken together, these data give new insights into mechanisms governing IGF-1 signaling in breast cancer.
