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Title: MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells
Author: Sánchez-Cid Pérez, Lourdes
Pons, Mònica
Lozano Salvatella, Juan José
Rubio, Nuria
Guerra-Rebollo, Marta
Soriano, Aroa
Paris-Coderch, Laia
Segura, Miquel F.
Fueyo, Raquel
Arguimbau, Judit
Zodda, Erika
Bermudo, Raquel
Alonso, Immaculada
Caparrós, Xavier
Cascante i Serratosa, Marta
Rafii, Arash
Kang, Yibin
Martínez-Balbás, Marian
Weiss, Stephen J.
Blanco Fernández, Jerónimo
Muñoz, Montserrat
Fernández Ruiz, Pedro Luis
Thomsom, Timothy M.
Keywords: Micro RNAs
Càncer de mama
Cèl·lules epitelials
Breast cancer
Epithelial cells
Issue Date: 7-Sep-2017
Publisher: Impact Journals
Abstract: MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR-200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.
Note: Reproducció del document publicat a:
It is part of: Oncotarget, 2017, vol. 8, num. 48
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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