A Splice Variant of HER2 Activates Key Signaling Cascades and Evokes Mammary Tumors and Metastases

ABSTRACT: The Epidermal Growth Factor Receptor 2 (ERBB2 or HER2) is amplified and overexpressed in approximately 20% of invasive breast cancers and is associated with metastasis and poor prognosis. Here we describe the role of a constitutively active splice variant of HER2 (Delta-HER2) in human mammary epithelial cells. Overexpression of Delta-HER2 in human mammary cells decreased apoptosis and increased proliferation and expression of epithelial-to-mesenchymal markers. It also induced invasion in three-dimensional cultures and promoted tumorigenicity and metastasis in vivo. In contrast, similar overexpression of wild-type HER2 failed to evoke the same effects. Unbiased protein-tyrosine phosphorylation profiling revealed a significant increase in phosphorylation of several key signaling proteins upo

ORGANISM(S): Homo sapiens

SUBMITTER: Tim Roloff 

PROVIDER: E-GEOD-42781 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress