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Breast Cancer Research
Published in: Breast Cancer Research 4/2010

Open Access 01-08-2010 | Research article

MYBsuppresses differentiation and apoptosis of human breast cancer cells

Authors: Yvette Drabsch, Robert G Ramsay, Thomas J Gonda

Published in: Breast Cancer Research | Issue 4/2010

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Abstract

Introduction

MYB is highly expressed in estrogen receptor positive (ER + ve) breast tumours and tumour cell lines. We recently demonstrated that MYB is essential for the proliferation of ER + ve breast cancer cells, and have now investigated its role in mammary epithelial differentiation.

Methods

MCF-7 breast cancer cells were treated with sodium butyrate, vitamin E succinate or 12-O-tetradecanoylphorbol-13-acetate to induce differentiation as measured by Nile Red staining of lipid droplets and β-casein expression. The non-tumorigenic murine mammary epithelial cell (MEC) line, HC11, was induced to differentiate with lactogenic hormones. MYB levels were manipulated by inducible lentiviral shRNA-mediated knockdown and retroviral overexpression.

Results

We found that MYB expression decreases following chemically-induced differentiation of the human breast cancer cell line MCF-7, and hormonally-induced differentiation of a non-tumorigenic murine mammary epithelial cell (MEC) line, HC11. We also found that shRNA-mediated MYB knockdown initiated differentiation of breast cancer cells, and greatly sensitised them to the differentiative and pro-apoptotic effects of differentiation-inducing agents (DIAs). Sensitisation to the pro-apoptotic effects DIAs is mediated by decreased expression of BCL2, which we show here is a direct MYB target in breast cancer cells. Conversely, enforced expression of MYB resulted in the cells remaining in an undifferentiated state, with concomitant suppression of apoptosis, in the presence of DIAs.

Conclusions

Taken together, these data imply that MYB function is critical in regulating the balance between proliferation, differentiation, and apoptosis in MECs. Moreover, our findings suggest MYB may be a viable therapeutic target in breast cancer and suggest specific approaches for exploiting this possibility.
Appendix
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Metadata
Title
MYBsuppresses differentiation and apoptosis of human breast cancer cells
Authors
Yvette Drabsch
Robert G Ramsay
Thomas J Gonda
Publication date
01-08-2010
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2010
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2614

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