Abstract A45: Regulatory network of the metastatic process in breast cancer

Breast cancer (BC) is a heterogeneous disease composed of multiple subtypes with different molecular characteristics and clinical outcomes. In Brazil, this neoplasia is the first cause of cancer death in women, mainly due to the diagnosis in advanced stages, when the possibility of the development of metastases is greater. The metastatic process is related to expression of the epithelial-to-mesenchymal transition transcription factors (EMT-TFs) SNAIL, SLUG, SIP1, and TWIST1. Recently, we have described the role of NF-kB as a regulator of the gene expression of TWIST1, SLUG, and SIP1 factors in aggressive BC cells HCC-1954 (Her2/neu positive) and MDA-MB-231 (triple negative, TN). Through bioinformatics tools, we identified several binding sites for NF-kB in the promoter region of these genes that were confirmed by chromatin immunoprecipitation and luciferase reporter assays. In order to support our findings, we evaluated the expression of NF-kB, Twist, Slug, and Sip1 through RT-qPCR on breast tumor samples. A comparison among the breast cancer subtypes indicated that TN group expressed significantly more NF-kB/p65, Slug, and Sip1. We also observed elevated levels of Twist1 on HER2 than other subtypes. Then, for each tumor sample, mRNA levels for NF-kB/p65 were plotted versus mRNA levels for Slug, Twist, and Sip1. Statistical analysis using the Pearson method showed a clear positive correlation between NF-kB and Twist (r = 0.923; P Citation Format: Bruno R. B. Pires, Gerson M. Ferreira, Renata Binato, Eliana Abdelhay. Regulatory network of the metastatic process in breast cancer [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; Sao Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A45.