Please use this identifier to cite or link to this item:
Title: miR-424(322)/503 is a breast cancer tumor suppressor whose loss promotes resistance to chemotherapy
Author: Rodriguez-Barrueco, Ruth
Nekritz, Erin A.
Bertucci, François
Yu, Jiyang
Sanchez-Garcia, Félix
Zeleke, Tizita Z.
Gorbatenko, Andrej
Birnbaum, Daniel
Ezhkova, Elena
Cordon Cardo, Carlos
Finetti, Pascal
Llobet-Navas, David
Silva, Jose M.
Keywords: Càncer de mama
Micro RNAs
Breast cancer
Issue Date: 15-Mar-2017
Publisher: Cold Spring Harbor Laboratory Press
Abstract: The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy. Here, through the analysis of ∼3000 primary tumors, we show that miR-424(322)/503 is commonly lost in a subset of aggressive breast cancers and describe the genetic aberrations that inactivate its expression. Furthermore, through the use of a knockout mouse model, we demonstrate for the first time that loss of miR-424(322)/503 promotes breast tumorigenesis in vivo. Remarkably, we found that loss of miR-424(322)/503 promotes chemoresistance due to the up-regulation of two of its targets: BCL-2 and insulin-like growth factor-1 receptor (IGF1R). Importantly, targeted therapies blocking the aberrant activity of these targets restore sensitivity to chemotherapy. Overall, our studies reveal miR-424(322)/503 as a tumor suppressor in breast cancer and provide a link between mammary epithelial involution, tumorigenesis, and the phenomenon of chemoresistance.
Note: Reproducció del document publicat a:
It is part of: Genes & Development, 2017, vol. 31, num. 6, p. 553-566
Related resource:
ISSN: 0890-9369
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

Files in This Item:
File Description SizeFormat 
694921.pdf1.87 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.