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Insulin-Like Growth Factor-1 Signaling Regulates miRNA Expression in MCF-7 Breast Cancer Cell Line
Authors:Elizabeth C. Martin  Melyssa R. Bratton  Yun Zhu  Lyndsay V. Rhodes  Syreeta L. Tilghman  Bridgette M. Collins-Burow  Matthew E. Burow
Affiliation:1. Department of Medicine-Section of Hematology and Medical Oncology, Tulane University, New Orleans, Louisiana, United States of America.; 2. Department of Pharmacology, Tulane University, New Orleans, Louisiana, United States of America.; 3. College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana, United States of America.; Baylor College of Medicine, United States of America,
Abstract: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.
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