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The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling.

Moreira Sousa C, McGuire JR, Thion MS, Gentien D, de la Grange P, Tezenas du Montcel S, Vincent-Salomon A, Durr A, Humbert S - EMBO Mol Med (2013)

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.

View Article: PubMed Central - PubMed

Affiliation: Institut Curie, Paris, France; CNRS UMR 3306, Orsay, France.

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PolyQ-huntingtin causes differential gene expression in tumoursA. Venn diagram for genes found to be regulated using Mouse Exon 1.0 ST Affymetrix array chips in 4 MMTV-PyVT/HdhQ111/Q111versus 4 MMTV-PyVT/HdhQ7/Q7 tumours (6 weeks after detection), which met the criteria of a p-value < 0.05 and a fold-change of more than 1.5.B–D. Hierarchical clustering for ECM remodelling (B), cytoskeleton associated (C), and proliferation/cell death genes (D). WT: MMTV-PyVT/HdhQ7/Q7 tumours; polyQ: MMTV-PyVT/HdhQ111/Q111 tumours.E. mRNA levels of huntingtin as determined by quantitative PCR analysis in 4 MMTV-PyVT/HdhQ7/Q7 and 3 MMTV-PyVT/HdhQ111/Q111 tumours (*p-value = 0.0165).
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fig02: PolyQ-huntingtin causes differential gene expression in tumoursA. Venn diagram for genes found to be regulated using Mouse Exon 1.0 ST Affymetrix array chips in 4 MMTV-PyVT/HdhQ111/Q111versus 4 MMTV-PyVT/HdhQ7/Q7 tumours (6 weeks after detection), which met the criteria of a p-value < 0.05 and a fold-change of more than 1.5.B–D. Hierarchical clustering for ECM remodelling (B), cytoskeleton associated (C), and proliferation/cell death genes (D). WT: MMTV-PyVT/HdhQ7/Q7 tumours; polyQ: MMTV-PyVT/HdhQ111/Q111 tumours.E. mRNA levels of huntingtin as determined by quantitative PCR analysis in 4 MMTV-PyVT/HdhQ7/Q7 and 3 MMTV-PyVT/HdhQ111/Q111 tumours (*p-value = 0.0165).

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.


The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling.

Moreira Sousa C, McGuire JR, Thion MS, Gentien D, de la Grange P, Tezenas du Montcel S, Vincent-Salomon A, Durr A, Humbert S - EMBO Mol Med (2013)

PolyQ-huntingtin causes differential gene expression in tumoursA. Venn diagram for genes found to be regulated using Mouse Exon 1.0 ST Affymetrix array chips in 4 MMTV-PyVT/HdhQ111/Q111versus 4 MMTV-PyVT/HdhQ7/Q7 tumours (6 weeks after detection), which met the criteria of a p-value < 0.05 and a fold-change of more than 1.5.B–D. Hierarchical clustering for ECM remodelling (B), cytoskeleton associated (C), and proliferation/cell death genes (D). WT: MMTV-PyVT/HdhQ7/Q7 tumours; polyQ: MMTV-PyVT/HdhQ111/Q111 tumours.E. mRNA levels of huntingtin as determined by quantitative PCR analysis in 4 MMTV-PyVT/HdhQ7/Q7 and 3 MMTV-PyVT/HdhQ111/Q111 tumours (*p-value = 0.0165).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569645&req=5

fig02: PolyQ-huntingtin causes differential gene expression in tumoursA. Venn diagram for genes found to be regulated using Mouse Exon 1.0 ST Affymetrix array chips in 4 MMTV-PyVT/HdhQ111/Q111versus 4 MMTV-PyVT/HdhQ7/Q7 tumours (6 weeks after detection), which met the criteria of a p-value < 0.05 and a fold-change of more than 1.5.B–D. Hierarchical clustering for ECM remodelling (B), cytoskeleton associated (C), and proliferation/cell death genes (D). WT: MMTV-PyVT/HdhQ7/Q7 tumours; polyQ: MMTV-PyVT/HdhQ111/Q111 tumours.E. mRNA levels of huntingtin as determined by quantitative PCR analysis in 4 MMTV-PyVT/HdhQ7/Q7 and 3 MMTV-PyVT/HdhQ111/Q111 tumours (*p-value = 0.0165).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Institut Curie, Paris, France; CNRS UMR 3306, Orsay, France.

Show MeSH
Related in: MedlinePlus