Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profile in breast cancer cells with opposing responses to TGF-beta

ABSTRACT: We aim to test whether our panel of breast cancer cell lines belong to the claudinlow subtype of breast cancer using the classifier published by Prat et al. Breast Cancer Research 12, 2010. For the analysis, we used gene expression data of our cell lines obtained with Illumina bead arrays grown in 2D as attahed and in 3D as mammosphere cultures.

ORGANISM(S): Homo sapiens

SUBMITTER: Alejandra Bruna

PROVIDER: E-MTAB-1190 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TGFβ induces the formation of tumour-initiating cells in claudinlow breast cancer.

Bruna Alejandra A Greenwood Wendy W Le Quesne John J Teschendorff Andrew A Miranda-Saavedra Diego D Rueda Oscar M OM Sandoval Jose L JL Vidakovic Ana Tufegdzic AT Saadi Amel A Pharoah Paul P Stingl John J Caldas Carlos C

Nature communications 20120101

The role of transforming growth factor-beta (TGFβ) in the progression of different molecular subtypes of breast cancer has not been clarified. Here we show that TGFβ increases breast tumour-initiating cell (BTIC) numbers but only in claudin(low) breast cancer cell lines by orchestrating a specific gene signature enriched in stem cell processes that predicts worse clinical outcome in breast cancer patients. NEDD9, a member of the Cas family of integrin scaffold proteins, is necessary to mediate t ...[more]

PMID: 22968701

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Project description:Introduction: Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism. Methods: We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in-silico predictions for regulatory potential and disruption of transcription factor binding, and were functionally analysed in-vitro and in-vivo in normal and breast cancer cell lines. SNPs tagging the expression haplotypes were correlated with the total expression of several genes in breast tissue measured by Taqman and microarray technologies. The effect of the expression haplotypes on breast cancer risk in BRCA2 mutation carriers was investigated in 2754 carriers. Results: We identified common haplotypes associated with differences in the levels of BRCA2 expression in human breast cells. We characterised three cis-regulatory SNPs located at the promoter and two intronic regulatory elements, which affect the binding of the transcription factors C/EBPα, HMGA1, DBP and ZF5. We showed that the expression haplotypes also correlated with changes in the expression of other genes in normal breast. Furthermore, there was suggestive evidence that the minor allele of SNP rs4942440, which is associated with higher BRCA2 expression, is also associated with a reduced risk of breast cancer (per-allele HR=0.85, 95%CI=0.72-1.00, P-trend=0.048). Conclusion: Our work provides further insights into the role of cis-regulatory variation in the penetrance of disease-causing mutations. We identified small-effect genetic variants associated with allelic expression differences in BRCA2, which could possibly affect the risk in mutation carriers through altering expression levels of the wild-type allele. Total gene expression of normal breast sample from healthy controls. This submission represents transcriptome component of study.

Dataset Information

Gene expression profile in breast cancer cells with opposing responses to TGF-beta

Publications

TGFβ induces the formation of tumour-initiating cells in claudinlow breast cancer.

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