BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

Naderi, Ali, Liu, Ji and Bennett, Ian C. (2010) BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer. International Journal of Cancer, 126 7: 1596-1610. doi:10.1002/ijc.24866

Author Naderi, Ali
Liu, Ji
Bennett, Ian C.
Title BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2010-04
Year available 2009
Sub-type Article (original research)
DOI 10.1002/ijc.24866
Volume 126
Issue 7
Start page 1596
End page 1610
Total pages 15
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2011
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
0601 Biochemistry and Cell Biology
111201 Cancer Cell Biology
Abstract We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide-induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro-apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl-2 protein family, which involves the positive regulation of anti-apoptotic member Bcl-2 and the negative regulation of pro-apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl-2/NF-kappa B pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2-mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer. © 2009 UICC.
Keyword BEX2
Mitochondrial apoptosis
G1 arrest
Breast cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 26 AUG 2009

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
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Created: Sun, 14 Mar 2010, 00:04:53 EST