In Vitro and In Vivo Analysis of B-Myb in Basal-Like Breast Cancer

The basal-like breast cancer subtype portends a poor clinical prognosis, and a defining feature of this subtype is the high expression of genes in the “proliferation signature”. B-Myb, a member of the MYB protein family of transcription factors, is highly expressed in the proliferation signature and is amplified and overexpressed in a variety of tumor types, including breast. In this report we demonstrated that B-Myb is highly expressed in basal-like breast cancer relative to the other subtypes, and B-Myb expression alone is prognostic. We also identified an association between a nonsynonymous B-Myb germline variant (S427G, rs2070235) and an increased risk of having a basal-like breast cancer among patients with breast cancer. The expression of B-Myb, or the S427G variant, was manipulated in vitro and we observed that in hTERT-immortalized normal Human Mammary Epithelial Cells, but not basal-like tumor-derived lines, cells ectopically expressing B-Myb showed increased sensitivity to DNA topoisomerase II inhibitors, but not other chemotherapeutics; in addition, microarray analyses of B-Myb overexpressing cells identified many G2/M targets as being preferentially induced. These results again suggest that B-Myb is involved in G2/M cell cycle control and that dysregulation of B-Myb may contribute to an increased sensitivity to a specific class of chemotherapeutic agents in vitro, and potentially in vivo. These data provide insight into the influence of B-Myb in human breast cancer, which is of potential clinical importance for determining disease risk and for guiding treatment. Keywords: MYB protein family of transcription factors in Breast Cancer subtype study Reference VS. Samples