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| Home > Articles > Published articles > MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells |
| Home > Articles > Published articles > MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells |
(Hospital Universitari Vall d'Hebron. Institut de Recerca)| Date: | 2017 |
| 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. |
| Grants: | Ministerio de Ciencia e Innovación FIS/PI080274 Ministerio de Economía y Competitividad SAF2012-40017-C02-02 Ministerio de Economía y Competitividad RD12-0036-0036 Ministerio de Ciencia e Innovación SAF2011/24686 Ministerio de Economía y Competitividad SAF2012/40017-C02-01 Ministerio de Economía y Competitividad SAF2015/66984-C2-1-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR1482 Ministerio de Economía y Competitividad RD12-0037-0016 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR660 Instituto de Salud Carlos III RD09-0076-0038 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | MicroRNAs ; MiR-200 ; Epithelial reprogramming ; Progenitor luminal cells ; Invasive ductal breast cancer |
| Published in: | Oncotarget, Vol. 8, Num. 48 (October 2017) , p. 83384-83406, ISSN 1949-2553 |
