乳腺癌是由于恶性肿瘤侵略并破坏乳房正常组织而形成的癌变肿瘤,也可能扩散到其他地方,是全世界女性最常见的癌病,世界一年约有50万人死于乳腺癌。美国研究者对IGF-1调控乳腺癌miRNA表达的机制进行了系统研究*,研究结果发表在11月30日的PLoS ONE上。
MiRNA在肿瘤的发展和转变中起着重要调控作用,调控肿瘤细胞增殖,分化和细胞凋亡。许多miRNA表达受信号分子调控,如生长因子和激素分子等。在乳腺癌中,胰岛素样生长因子-1(Insulin-like Growth Factor 1,IGF-1)可作为促细胞分裂剂,能通过调控MAPK和PI3K/AKT信号通路,促进细胞增殖和凋亡,转而促进肿瘤的发生。
本研究中,研究人员利用miRNA表达谱芯片找到了一组已知的抑癌和致癌microRNA(miRNA)可由IGF-1信号因子直接调控(由联川生物提供miRNA芯片检测服务)。在进行IGF-1刺激前,选择性地抑制MAPK或AKT通路,可阻止抑癌miRNA的表达。研究人员首次发现在雌激素受体阳性的MCF-7乳癌细胞系内直接由IGF-1信号通路调控的miRNA, 并且证实了激酶信号通路可以调控一小组miRNA的表达。
本研究给出乳腺癌中IGF-1信号调控机制的新发现,对深入了解乳腺癌的发生,发展机制起着重要作用。(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.