Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human basal-like breast cancer - in vitro and in vivo Analysis of B-Myb

ABSTRACT: 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 âproliferation signatureâ. 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. Experiment Overall Design: Reference VS. Samples

ORGANISM(S): Homo sapiens

SUBMITTER: Charles Perou

PROVIDER: E-GEOD-11429 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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In vitro and in vivo analysis of B-Myb in basal-like breast cancer.

Thorner A R AR Hoadley K A KA Parker J S JS Winkel S S Millikan R C RC Perou C M CM

Oncogene 20081201 5

A defining feature of basal-like breast cancer, a breast cancer subtype with poor clinical prognosis, is the high expression of 'proliferation signature' genes. We identified B-Myb, a MYB family transcription factor that is often amplified and overexpressed in many tumor types, as being highly expressed in the proliferation signature. However, the roles of B-Myb in disease progression, and its mammary-specific transcriptional targets, are poorly understood. Here, we showed that B-Myb expression ...[more]

PMID: 19043454

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