MYB suppresses differentiation and apoptosis of human breast cancer cells

Drabsch, Y., Ramsay, R. G. and Gonda, T. J. (2010) MYB suppresses differentiation and apoptosis of human breast cancer cells. Breast Cancer Research, 12 4: R55-1-R55-17. doi:10.1186/bcr2614

Author Drabsch, Y.
Ramsay, R. G.
Gonda, T. J.
Title MYB suppresses differentiation and apoptosis of human breast cancer cells
Formatted title
MYB suppresses differentiation and apoptosis of human breast cancer cell
Journal name Breast Cancer Research   Check publisher's open access policy
ISSN 1465-5411
Publication date 2010-07-26
Sub-type Article (original research)
DOI 10.1186/bcr2614
Open Access Status DOI
Volume 12
Issue 4
Start page R55-1
End page R55-17
Total pages 17
Place of publication London, United Kingdom
Publisher Current Medicine Group
Collection year 2011
Language eng
Formatted 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-Otetradecanoylphorbol-13-acetate to induce differentiation as measured by Nile Red staining of lipid droplets and bcasein 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.

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 differentiationinducing 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.
Keyword Histone deacetylase inhibitors
BCL-2 expression
Sodium butyrate
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number R55

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
UQ Diamantina Institute - Open Access Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 33 times in Scopus Article | Citations
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Created: Sun, 30 Jan 2011, 00:06:44 EST