Type

Journal Article

Authors

A M Hopkins
L S Young
A D K Hill
E W Kay
L Hudson
E A McSherry
K Brennan

Subjects

Biochemistry

Topics
protein adhesion breast cancer human epidermal growth factor receptor 2 cell adhesion regulator protein junctional adhesion molecule a endothelial cells cell lines

Junctional adhesion molecule-A is co-expressed with HER2 in breast tumors and acts as a novel regulator of HER2 protein degradation and signaling. (2012)

Abstract Junctional adhesion molecule-A (JAM-A) is a membranous cell-cell adhesion protein involved in tight-junction formation in epithelial and endothelial cells. Its overexpression in breast tumors has recently been linked with increased risk of metastasis. We sought to identify if JAM-A overexpression was associated with specific subtypes of breast cancer as defined by the expression of human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER) and progesterone receptor. To this end, JAM-A immunohistochemistry was performed in two breast cancer tissue microarrays. In parallel, cross-talk between JAM-A, HER2 and ER was examined in several breast cell lines, using complementary genetic and pharmacological approaches. High JAM-A expression correlated significantly with HER2 protein expression, ER negativity, lower patient age, high-grade breast cancers, and aggressive luminal B, HER2 and basal subtypes of breast cancer. JAM-A and HER2 were co-expressed at high levels in vitro in SKBR3, UACC-812, UACC-893 and MCF7-HER2 cells. Knockdown or functional antagonism of HER2 did not alter JAM-A expression in any cell line tested. Interestingly, however, JAM-A knockdown decreased HER2 and ER-α expression, resulting in reduced levels of phospho-(active) AKT without an effect on the extracellular signal-related kinase phosphorylation. The downstream effects of JAM-A knockdown on HER2 and phospho-AKT were partially reversed upon treatment with the proteasomal inhibitor MG132. We conclude that JAM-A is co-expressed with HER2 and associates with aggressive breast cancer phenotypes. Furthermore, we speculate that JAM-A may regulate HER2 proteasomal degradation and activity, potentially offering a promise as a therapeutic target in HER2-positive breast cancers.Oncogene advance online publication, 2 July 2012; doi:10.1038/onc.2012.276.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

A M Hopkins, L S Young, A D K Hill, E W Kay, L Hudson, E A McSherry, K Brennan

Experts in our system

1
Ann M Hopkins
Royal College of Surgeons in Ireland
Total Publications: 26
 
2
Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
 
3
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110
 
4
Elaine W Kay
Royal College of Surgeons in Ireland
Total Publications: 157
 
5
Lance Hudson
Royal College of Surgeons in Ireland
Total Publications: 11