Abstract P5-05-05: The role and regulation mechanism of HOXB5 in human breaset cancer cells

Abstract

Abstract HOX genes are transcription factors that play important roles in body patterning and cell fate specification during normal development. Among of these, HOXB5, is involved in a variety of developmental processes, particularly during the enteric nervous system (ENS) development, and thus, abnormalities in HOXB5 function during embryo stages lead to Hirschsprung's disease. Importantly, many HOX genes, including HOXB5, are expressed not only during embryogenesis but also in adults and are dysregulated in various cancers. In a previous study, we found aberrant overexpression of HOXB5 in breast cancer tissues and cell lines and demonstrated that HOXB5 is important in the regulation of cell proliferation in breast cancer cells. Also, HOXB5 induces invasive potential through epithelial-mesenchymal transition (EMT). The relationship between HOXB5 and phenotypic changes in MCF7 breast cancer cells has been studied, however, HOXB5 functions as a transcription factor and its involvement in signaling pathways remain unclear. In this study, we selected putative downstream target genes of HOXB5, such as interleukin (IL)-6, Snail2 and epidermal growth factor receptor (EGFR) by PCR array analysis. These genes have been reported to be involved in cacner progression, which is characterised by increased growth speed and invasiveness of the tumor cells. Here, we discovered that HOXB5 transcriptionally upregulates the promoter activity of these genes. Chromatin immunoprecipitation (ChIP) analysis to confirm direct binding of HOXB5 to the promoter region is now ongoing. Since we found that HOXB5 induces EGFR protein expression and SRC phosphorylation, we will further investigate signaling pathway components to understand the underlying molecular mechanisms of HOXB5 action in breast cancer. Citation Format: Kim JM, Lee J-Y, Kim MH. The role and regulation mechanism of HOXB5 in human breaset cancer cells [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-05-05.