• 1 Department of General Surgery, Tianjin First Central Hospital, No.24, Fukang Road, Nankai District, Tianjin, 300204, China
  • 2 Innoscience Research Sdn Bhd, Suites B-5-7, Level 5, Sky Park @ One City, Jalan USJ 25/1, 47650, Subang Jaya, Selangor, Malaysia
  • 3 Department of Obstetrics and Gynecology, Maternity and Child Health Care of Zaozhuang, Zaozhuang, 277100, Shandong province, China
  • 4 Department of General Surgery, The Second Hospital of Shandong University, No.247 Beiyuan Road, Tianqiao District, Jinan City, Shandong Province, 250033, China.
Sci Rep, 2019 12 11;9(1):18844.
PMID: 31827114 DOI: 10.1038/s41598-019-54289-6


Resistance to tamoxifen is a major clinical challenge. Research in recent years has identified epigenetic changes as mediated by dysregulated miRNAs that can possibly play a role in resistance to tamoxifen in breast cancer patients expressing estrogen receptor (ER). We report here elevated levels of EMT markers (vimentin and ZEB1/2) and reduced levels of EMT-regulating miR-200 (miR-200b and miR-200c) in ER-positive breast cancer cells, MCF-7, that were resistant to tamoxifen, in contrast with the naïve parental MCF-7 cells that were sensitive to tamoxifen. Further, we established regulation of c-MYB by miR-200 in our experimental model. C-MYB was up-regulated in tamoxifen resistant cells and its silencing significantly decreased resistance to tamoxifen and the EMT markers. Forced over-expression of miR-200b/c reduced c-MYB whereas reduced expression of miR-200b/c resulted in increased c-MYB We further confirmed the results in other ER-positive breast cancer cells T47D cells where forced over-expression of c-MYB resulted in induction of EMT and significantly increased resistance to tamoxifen. Thus, we identify a novel mechanism of tamoxifen resistance in breast tumor microenvironment that involves miR-200-MYB signaling.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.