A functionally significant cross-talk between androgen receptor and ErbB2 pathways in Estrogen receptor negative breast cancer

Ali Naderi and Hughes-Davies, L. (2008) A functionally significant cross-talk between androgen receptor and ErbB2 pathways in Estrogen receptor negative breast cancer. Neoplasia, 10 6: 542-548. doi:10.1593/neo.08274


Author Ali Naderi
Hughes-Davies, L.
Title A functionally significant cross-talk between androgen receptor and ErbB2 pathways in Estrogen receptor negative breast cancer
Journal name Neoplasia   Check publisher's open access policy
ISSN 1522-8002
Publication date 2008-06-01
Year available 2008
Sub-type Article (original research)
DOI 10.1593/neo.08274
Open Access Status DOI
Volume 10
Issue 6
Start page 542
End page 548
Total pages 7
Place of publication The United States of America
Publisher Neoplasia Press
Language eng
Subject C1
111201 Cancer Cell Biology
920102 Cancer and Related Disorders
Abstract Recent studies have identified novel subgroups in ER-negative breast cancer based on the expression pattern of androgen receptor (AR). One subtype (molecular apocrine) has an over-expression of steroid-response genes and ErbB2. Using breast cancer cell lines with molecular apocrine features, we demonstrate a functional cross-talk between AR and ErbB2 pathways. We show that stimulation of AR and ErbB2 pathways leads to the cross-regulation of gene expression for AR, ErbB2, FOXA1, XBP1, TFF3, and KLK3. As opposed to the physiologic transient phosphorylation of extracellular signal-regulated kinase (ERK1/2) observed with the testosterone treatment, we demonstrate that the addition of ErbB2 inhibition leads to a persistent phosphorylation of ERK1/2, which negatively regulates the downstream signaling and cell growth. This suggests a mechanism for the cross-talk involving the ERK pathway. Moreover, testosterone stimulates the proliferation of molecular apocrine breast cell lines, and this effect can be reversed using antiandrogen flutamide and anti-ErbB2 AG825. Conversely, the growth stimulatory effect of heregulin can also be inhibited with flutamide, suggesting a cross-talk between the AR and ErbB2 pathways affecting cell proliferation. Importantly, there is a synergy with the combined use of flutamide and AG825 on cell proliferation and apoptosis, which indicates a therapeutic advantage in the combined blockage of AR and ErbB2 pathways. Copyright
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Tue, 24 Mar 2009, 22:42:48 EST by Kylie Hengst on behalf of UQ Diamantina Institute