A feedback loop between BEX2 and ErbB2 mediated by c-Jun signaling in breast cancer

Naderi, Ali, Liu, Ji and Francis, Glenn D. (2012) A feedback loop between BEX2 and ErbB2 mediated by c-Jun signaling in breast cancer. International Journal of Cancer, 130 1: 71-82. doi:10.1002/ijc.25977

Author Naderi, Ali
Liu, Ji
Francis, Glenn D.
Title A feedback loop between BEX2 and ErbB2 mediated by c-Jun signaling in breast cancer
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2012-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1002/ijc.25977
Volume 130
Issue 1
Start page 71
End page 82
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2012
Language eng
Formatted abstract
BEX2 is a member of brain expressed X-linked gene family that is differentially expressed in primary breast tumors. We have previously demonstrated that BEX2 expression protects breast cancer cells against mitochondrial apoptosis and G1 cell cycle arrest. In addition, we have shown that BEX2 is a c-Jun target gene and, in turn, regulates the phosphorylation of c-Jun in breast cancer cells. In our study, we investigated BEX2 protein expression in a tissue microarray cohort of 225 breast tissue samples with known clinical, pathological and biomarker information. We observed that BEX2 protein was overexpressed in ∼50% of malignant breast tumors compared to only 7% of benign breast samples. Notably, BEX2 positive tumors identified a subset of breast cancers with the overexpression of ErbB2 and phosphorylated c-Jun proteins. Furthermore, using in vitro models, we demonstrated that the mechanism of this association is a functional feedback loop involving ErbB2, c-Jun and BEX2 in breast cancer cells. In this feedback loop, ErbB2 overexpression results in an induction of c-Jun and BEX2 expression. Importantly, ErbB2 induction of BEX2 expression was abrogated by a dominant-negative mutant of c-Jun, suggesting that this effect was mediated through the regulation of c-Jun signaling. In turn, the overexpression of BEX2 led to an increase in both c-Jun–mediated induction of ErbB2 and c-Jun binding to the ErbB2 promoter in MCF-7 cells. Our study suggests that BEX2 protein is overexpressed in approximately half of breast cancers and has a positive feedback loop with ErbB2 mediated by c-Jun signaling in breast cancer cells.
Keyword BEX2
Breast cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 20 APR 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Fri, 14 Oct 2011, 11:50:20 EST by Dr Ali Naderi on behalf of UQ Diamantina Institute