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

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. 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. 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 β1-integrin signaling pathway was probably responsible for this phenomenon. 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 β1-integrin signaling pathway. Thus, ITGB1 may be a potential target for the improvement of anti-hormone therapy reaction in ER(+) breast cancer patients.

Hu S ，Yang Q ，Chen Z ，Fu W ... -  《-》

Acquisition of epithelial-mesenchymal transition phenotype in the tamoxifen-resistant breast cancer cell: a new role for G protein-coupled estrogen receptor in mediating tamoxifen resistance through cancer-associated fibroblast-derived fibronectin and β1-

Yuan J ，Liu M ，Yang L ，Tu G ，Zhu Q ，Chen M ，Cheng H ，Luo H ，Fu W ，Li Z ，Yang G ... -  《-》

Proteomic analysis of acquired tamoxifen resistance in MCF-7 cells reveals expression signatures associated with enhanced migration.

Zhou C ，Zhong Q ，Rhodes LV ，Townley I ，Bratton MR ，Zhang Q ，Martin EC ，Elliott S ，Collins-Burow BM ，Burow ME ，Wang G ... -  《-》

Loss of pigment epithelium-derived factor: a novel mechanism for the development of endocrine resistance in breast cancer.

Jan R ，Huang M ，Lewis-Wambi J 《-》

Activating transcription factor-2 (ATF2) is a key determinant of resistance to endocrine treatment in an in vitro model of breast cancer.

Giannoudis A ，Malki MI ，Rudraraju B ，Mohhamed H ，Menon S ，Liloglou T ，Ali S ，Carroll JS ，Palmieri C ... -  《-》