BioProject

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. More...

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. Knockdown of the miR-200 target, ZEB2, partially phenocopied the expression of miR200s with a strong enhancement of mammosphere growth and ALDH activity. 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. Overall design: Microarray expression screening was performed using tissue samples from 8 ductal carcinomas in situ (DCIS), 20 primary IDC without LN involvement (PNM), 20 primary IDC with regional LN involvement (PM), 20 LN metastases matched to the node-positive primary tumors (LNM) and 20 distant metastases (DM) and a pool of 10 normal breast epithelial tissues (N). Less...