Abstract 2248: The Y-box-binding protein 1 is associated with breast cancer progression and metastasis

Abstract

Abstract The Y-box-binding protein 1 (YB-1) which belongs to the RNA- and DNA-binding protein family with a conserved cold-shock domain, is known to regulate transcription and translation. Extensive studies carried out on the multi-functional YB-1 protein have implicated its role in tumor growth and drug resistance. However, the association between YB-1 and breast cancer metastasis has not been fully investigated. To determine if YB-1 expression is correlated with breast cancer progression, we evaluated protein expression analysis in breast cancer tissue microarrays from the Singapore General Hospital by immunohistochemistry using an N-terminal YB-1 antibody and gene expression analysis in a TissueScan breast cancer tissue qPCR array (a rapid-scan cDNA panel of 48 breast cancer tissues representing breast cancer in different tumor stages) by real time RT-PCR. Next, we down-regulated the expression of the YB-1 protein in MDA-MB-231 breast cancer cells by si-RNA mediated silencing of the YB-1 gene and performed migration assays (using polycarbonate membranes of transwells separating the upper and lower chambers in 24-well plates) and invasion assays (using Matrigel-coated transwell chambers). The results show that 88.7% of breast cancer tissues were positively immunostained for the YB-1 protein and a higher YB-1 expression level was associated with axillary lymph node spread. YB-1 gene expression level in the breast cancer tissues was also higher in the advance stages of breast cancer as compared to the early stage of the tumor. In the in vitro experiments, the silencing efficiency of the YB-1 siRNA was around 90% and significant down-regulation of the YB-1 protein was verified by Western blot analysis and immunostaining of the MDA-MB-231 cells. Furthermore, siYB-1 mediated knockdown of YB-1 expression significantly reduced the migration ability and invasive potential of MDA-MB-231 cells as compared to the control group. Collectively, the data obtained from breast cancer tissues and in vitro experiments has provided evidence that YB-1 expression is associated with aggressive behavior in breast cancer. It would seem that YB-1 is a potential biomarker of metastasis in breast cancer and a promising molecular target in breast cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2248.