Jab1 is a target of EGFR signaling in ERα-negative breast cancer

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dc.contributor.author Wang, Jiaxu
dc.contributor.author Barnes, Rebecca O
dc.contributor.author West, Nathan R
dc.contributor.author Olson, Melanie
dc.contributor.author Chu, Jenny E
dc.contributor.author Watson, Peter H
dc.date.accessioned 2014-08-18T20:48:48Z
dc.date.available 2014-08-18T20:48:48Z
dc.date.copyright 2008 en_US
dc.date.issued 2008-06-06
dc.identifier.citation Wang et al.: Jab1 is a target of EGFR signaling in ERα-negative breast cancer. Breast Cancer Research 2008, 10:R51. en_US
dc.identifier.uri http://breast-cancer-research.com/content/10/3/R51
dc.identifier.uri http://dx.doi.org/10.1186/bcr2105
dc.identifier.uri http://hdl.handle.net/1828/5567
dc.description BioMed Central en_US
dc.description.abstract Introduction c-Jun activation domain-binding protein-1 (Jab1) is a multifunctional signaling protein that previously has been shown to be a master regulator of a poor prognostic gene signature in invasive breast cancer and to mediate the action of S100A7. Since epidermal growth factor receptor (EGFR), like S100A7, is often expressed in estrogen receptor-alphanegative (ERα-) breast cancer, we set out to investigate the role of Jab1 in mediating EGFR signaling, another facet of the ERα- phenotype. Methods MDA-MB-231 and MDA-MB-468 ERα-/EGFR+ cell lines were assessed for localization of Jab1 and levels of downstream genes by immunofluorescence and nuclear protein extract assay following treatment with epidermal growth factor (EGF) and extracellular signal-regulated kinase (ERK) pathway inhibitor. A cohort of 424 human breast tumors was also assessed by immunohistochemistry. Results EGF treatment of cell lines resulted in increased Jab1 nuclear expression. This effect was inhibited by the ERK pathway inhibitor, PD98059. EGF treatment was also associated with colocalization of pERK (phosphorylated ERK) and Jab1 as well as regulation of the Jab1 downstream target gene, p27. When Jab1 activity was knocked down, p27 levels were restored to pre-EGF treatment level. Analysis of EGFR and Jab1 expression in a cohort of invasive breast tumors by tissue microarray and immunohistochemistry confirmed a relationship between EGFR and increased nuclear Jab1 within the ERα- subset (n = 154, P = 0.019). The same association was also confirmed for S100A7 and Jab1 (P = 0.036), and high Jab1 nuclear expression was most frequent in tumors that were positive for both EGFR and S100A7 (P = 0.004). Conclusion Jab1 is a target of EGFR signaling in ERα- cell lines and breast tumors and therefore may be a common central factor and potential therapeutic target for important cell signaling pathways in ERα- breast cancer. en_US
dc.description.sponsorship PHW is supported by an operating grant from the Canadian Institutes of Health Research (CIHR) (grant number MOP-64349). JW is supported by a Michael Smith Foundation for Health Research Trainee Fellowship and by a Susan Komen for the Cure Postdoctoral Fellowship grant. This study was also supported by the BC Cancer Agency's Tumor Tissue Repository and the Manitoba Breast Tumor Bank, funded by a grant from the CIHR (grant number PRG80155), and supported by Cancer-Care Manitoba. en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.title Jab1 is a target of EGFR signaling in ERα-negative breast cancer en_US
dc.type Article en_US
dc.description.scholarlevel Faculty en_US
dc.description.reviewstatus Reviewed en_US

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