Affordable Access

Publisher Website

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

Authors
Journal
Oncogene
0950-9232
Publisher
Nature Publishing Group
Publication Date
Volume
28
Issue
5
Identifiers
DOI: 10.1038/onc.2008.430
Source
Legacy
Keywords
  • Article
Disciplines
  • Biology
  • Medicine

Abstract

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 demonstrated that B-Myb expression is a significant predictor of survival and pathological complete response to neoadjuvant chemotherapy in breast cancer patients. We also identified a significant association between the G/G genotype of a nonsynonymous B-Myb germline variant (rs2070235, S427G) and an increased risk of basal-like breast cancer [OR 2.0, 95% CI (1.1-3.8)]. In immortalized, human mammary epithelial cell lines, but not basal-like tumor lines, cells ectopically expressing wild-type B-Myb or the S427G variant showed increased sensitivity to two DNA topoisomerase IIα inhibitors, but not to other chemotherapeutics. In addition, microarray analyses identified many G2/M genes as being induced in B-Myb overexpressing cells. These results confirm that B-Myb is involved in cell cycle control, and that dysregulation of B-Myb may contribute to increased sensitivity to a specific class of chemotherapeutic agents. 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.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

FGFR signaling promotes the growth of triple-negat...

on Clinical Cancer Research Aug 15, 2011

Metaplastic breast carcinomas are basal-like breas...

on Breast Cancer Research and Tre... September 2009

Discovery of structure-based small molecular inhib...

on Breast Cancer Research and Tre... May 2014
More articles like this..