Department of Medicine-Section of Hematology and Medical Oncology, Tulane University, New Orleans, LA, USA.
PLoS One. 2012;7(11):e49067. doi: 10.1371/journal.pone.0049067. Epub 2012 Nov 30.
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.
在乳腺癌中，胰岛素样生长因子 1（IGF-1）水平的增加可以作为有丝分裂原通过调节 MAPK 和 AKT 信号通路来促进肿瘤发生。这两条信号通路的信号传导使 IGF-1 能够利用有利于增殖和细胞存活的机制。在这里，我们证明了先前描述的一组肿瘤抑制因子和致癌 microRNAs（miRNAs）受 IGF-1 信号的直接调节。此外，我们还表明，在 IGF-1 刺激之前选择性地抑制 MAPK 或 AKT 通路可防止先前描述的家族和簇特异性肿瘤抑制 miRNA 的表达。在这里，我们首次在雌激素受体阳性 MCF-7 乳腺癌细胞系中定义了受 IGF-1 信号直接调节的特定 miRNAs，并证明激酶信号传导是一小部分 microRNAs 表达的调节剂。总之，这些数据为乳腺癌中 IGF-1 信号的调控机制提供了新的见解。
