The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling.
Bottom Line: In agreement, mutant huntingtin accelerates epithelial to mesenchymal transition and enhances cell motility and invasion.Finally, we report that in HD, the dynamin dependent endocytosis of the ErbB2/HER2 receptor tyrosine kinase is reduced.This leads to its accumulation and to subsequent increases in cell motility and proliferation.
Affiliation: Institut Curie, Paris, France; CNRS UMR 3306, Orsay, France.Show MeSH
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Mentions: To decipher the molecular events that lead to the increased tumourigenesis associated with polyQ-huntingtin expression, we examined the gene expression patterns of MMTV-PyVT/HdhQ7/Q7 and MMTV-PyVT/HdhQ111/Q111 mammary tumours using Affymetrix Mouse Exon 1.0 ST microarrays (Fig 2). Out of 43,379 genes analysed in four samples of each type of tumour, 416 genes were found to be differentially regulated with fold differences of at least 1.5 (p-value < 0.05), and 171 of these encoded a known protein (Fig 2A and Supporting Information Table S1). Most of the genes affected by polyQ-huntingtin expression (73%) were up-regulated in the tumours expressing polyQ-huntingtin compared to their expression levels in the wild-type tumours (Supporting Information Fig S3A and Table S1). Hierarchical clustering analysis of regulated genes confirmed that the tumour samples could be assigned to two primary clusters of tumours (Fig. 2 and Supporting Information Fig S3A). The left group of the dendogram contained the control tumour samples and the right group the HD tumour samples, with replicates in each cluster demonstrating substantial expression pattern homogeneity.
Affiliation: Institut Curie, Paris, France; CNRS UMR 3306, Orsay, France.