{"database":"biostudies-other","file_versions":[],"scores":null,"additional":{"submitter":["Alajati A"],"pagination":["5320-5327"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-ECPF-GEOD-42781"],"project":["EurocanPlatform"],"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 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)."],"repository":["biostudies-other"],"experiment_type":["transcription profiling by array"],"data_source":["EurocanPlatform"],"omics_type":["Unknown"],"volume":["73"],"journal":["Cancer research"],"species":["Homo sapiens"],"pubmed_authors":["Voshol H","Duss S","Sausgruber N","Aceto N","Alajati A","Sarret S","Bonenfant D","Bentires-Alj M"],"additional_accession":[]},"is_claimable":false,"name":"A Splice Variant of HER2 Activates Key Signaling Cascades and Evokes Mammary Tumors and Metastases","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).","dates":{"release":"2016-04-14T14:18:17Z","publication":"2013 Sep","modification":"2016-04-14T14:18:17Z","creation":"2016-04-14T14:18:17Z"},"accession":"S-ECPF-GEOD-42781","cross_references":{"GEO":["GSE42781"],"ArrayExpress":["E-GEOD-42781"],"EFO":["EFO_0000305","EFO_0000322","EFO_0002660"],"ArrayExpress files":["E-GEOD-42781"]}}