Role of β1-integrin in promoting cell motility and tamoxifen resistance of human breast cancer MCF-7 cells

Background: The mechanism of acquired resistance of tamoxifen in endocrine therapy of breast cancer is not fully understood. In this study, we investigated the genomic changes in acquired tamoxifen-resistant cell lines. Methods: Tamoxifen-resistant subclones (MCF-7R) derived from parent MCF-7 cells, which is an ER(+) breast cancer cell line, cultured with 4-hydrotamoxifen more than 6 months were used to obtain genomic alterations. Cell growth, microarray, and quantitative real-time PCR (q-RTPCR) assays were conducted. Additionally, the ITGB1 function was investigated in MCF-7R cells and MCF-7R ITGB1-silenced subclones using MTT and Transwell assays. Online pathway analysis was performed to assess the genetic characteristics of tamoxifen resistance. Results: The gene expression profile of the tamoxifen-resistant cell line was considerably changed compared to the tamoxifen-sensitive cell line. Of 4102 genes with altered expressions, 1986 genes were upregulated, whereas 2116 were downregulated. The ITGB1 expression in MCF-7R cells was higher than that in MCF-7 cells. Interestingly, ITGB1 silencing partially rescued the sensitivity of MCF-7R cells to tamoxifen and reduced their motility. The activation of the beta 1-integrin signaling pathway was probably responsible for this phenomenon. Conclusions: Our data confirm the presence of alterations in the genes of tamoxifen-resistance breast cancer cells. ITGB1 probably partially contributes to tamoxifen resistance and cell motility via the beta 1-integrin signaling pathway. Thus, ITGB1 may be a potential target for the improvement of anti-hormone therapy reaction in ER(+) breast cancer patients.