Transcriptomics

Dataset Information

20

Distinct ErbB-2-coupled signalling pathways promote mammary tumors with unique pathological and transcriptional profiles


ABSTRACT: ErbB-2 overexpression and amplification occurs in 15 - 30% of human invasive breast carcinomas associated with poor clinical prognosis. Previously, we have demonstrated that four ErbB-2/Neu tyrosine-autophosphorylation sites within the cytoplasmic tail of the receptor recruit distinct adaptor proteins and are sufficient to mediate transforming signals in vitro. Two of these sites representing the Grb2 (Neu-YB) and Shc (Neu-YD) binding sites can induce mammary tumourigenesis and metastasis. Here we show that Neu-YC and Neu-YE transgenic mice develop metastatic mammary tumours. A detailed comparison of pathological and transcriptional profiles among all Neu mutant mouse models revealed that Neu-YC, -YD and -YE mammary tumours shared similar pathological and transcriptional features correlating with their capacity to signal through a common adaptor like Shc. In contrast, the Neu-YB mouse model displayed a unique pathology with a high metastatic potential that correlates with a distinct transcriptional profile. We identified genes specifically expressed in YB-induced mammary tumours, including CXCL12/SDF-1α that promotes malignant tumour progression. Furthermore, Neu-YB tumour epithelial cells showed abundant intracellular CXCL12/SDF-1α protein, which may reflect the more aggressive phenotype among all Neu mutant mouse models. These findings indicate that activation of distinct Neu-coupled signalling pathways has a deep impact on the biological behaviour of Neu-induced tumours. Keywords: genetic modification, Neu mutant mouse models, mammary tumor Overall design: Total RNA was isolated from 10 individual flash frozen mammary tumour samples derived from our MMTV/neundl-NYPD, -YB, -YC, -YD, -YE and the parental MMTV/neu NDL2-5 strains. Two RNA pools, containing equal amount of total RNA from five individual tumours, were generated from each strain and functioned as a biological repeat. Five hundred nanograms of total RNA from each pool was subjected to one round of T7 linear amplification using the Amino Allyl MessageAmpTM aRNA Kit (Ambion, Austin, Texas). Ten micrograms of the resulting aRNA was labelled with Cy3 and Cy5 dyes. Each of the 12 Samples represents a dyeswap pair.

INSTRUMENT(S): Agilent-012694 Whole Mouse Genome G4122A (Feature Number version)

ORGANISM(S): Mus musculus  

SUBMITTER: Daniela Cernea   

PROVIDER: GSE7595 | GEO | 2007-08-15

SECONDARY ACCESSION(S): PRJNA100181

REPOSITORIES: GEO

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