Microrna-9 and -224 In Trastuzumab Resistant HER2 Positive Breast Cancer Cells

ABSTRACT HER2 positive breast cancer accounts for approximately 25 % of all breast cancer cases. Trastuzumab, a humanised monoclonal antibody, is an approved established treatment for HER2 positive breast cancer; however, patients that initially respond frequently develop resistance. The aim of this study is to investigate microRNAs in cell line models of acquired and innate trastuzumab resistance. MicroRNA was extracted from the HER2 positive cells; SKBR3, BT474, and the acquired trastuzumab resistant variants SKBR3-T and BT474-T, and from a panel of innate trastuzumab sensitive (BT474, EFM-192A, SKBR3 and MDA-MB-361) or resistant cell lines (UACC-732, JIMT-1, HCC-202, HCC-1954, HCC1569 and MDA-MB-453), in triplicate. MicroRNA profiling was performed on SKBR3 and SKBR3-T using Taqman Low Density Arrays (TLDA). Differentially regulated miRNAs were selected using u003e 2-fold change and a P-value of  Conclusions This is the first report of the involvement of miR-9 and miR-224 in trastuzumab resistance in HER2 positive breast cancer. Preliminary functional studies suggest that miR-224 may play a role in regulating cell growth in HER2 positive breast cancer cells. Disclosure All authors have declared no conflicts of interest.