E-GEOD-42781 - A Splice Variant of HER2 Activates Key Signaling Cascades and Evokes Mammary Tumors and Metastases

Status
Released on 22 October 2013, last updated on 28 October 2013
Organism
Homo sapiens
Samples (9)
Array (1)
Protocols (7)
Description
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 upon Delta-HER2 expression, some of which not previously shown to belong to the HER2 pathway. In addition, microarray analysis revealed the expression of a set of genes specifically associated with Delta-HER2 expression. We found those genes to be highly expressed in ER-negative, high grade and metastatic primary breast tumors. Altogether, these results provide new insights into the function of a tumorigenic splice variant of HER2 and the signaling cascade deriving from its activity RNA was extracted from MCF10A expressing empty vector, WT-HER2 or Delta-HER2 (n=3).
Experiment type
transcription profiling by array 
Contacts
Tim Roloff <tim.roloff@fmi.ch>, Abdullah Alajati, Mohamed Bentires-Alj, Stephan Duss, Stephane Thiry, Tim C Roloff
Citation
Mammary tumor formation and metastasis evoked by a HER2 splice variant. Alajati A, Sausgruber N, Aceto N, Duss S, Sarret S, Voshol H, Bonenfant D, Bentires-Alj M. , Europe PMC 23867476
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-42781.idf.txt
Sample and data relationshipE-GEOD-42781.sdrf.txt
Raw data (1)E-GEOD-42781.raw.1.zip
Processed data (1)E-GEOD-42781.processed.1.zip
Array designA-AFFY-141.adf.txt
Links