Down-Regulation of miR-92 in Breast Epithelial Cells and in Normal but Not Tumour Fibroblasts Contributes to Breast Carcinogenesis.

Background: MicroRNA (miR) expression is commonly dysregulated in many cancers, including breast. MiR-92 is one of six miRs encoded by the miR-17-92 cluster, one of the best-characterised oncogenic miR clusters. We examined expression of miR-92 in the breast epithelium and stroma during breast cancer progression.

MiR-26b is down-regulated in carcinoma-associated fibroblasts from ER-positive breast cancers leading to enhanced cell migration and invasion.

Carcinoma-associated fibroblasts (CAFs) influence the behaviour of cancer cells but the roles of microRNAs in this interaction are unknown. We report microRNAs that are differentially expressed between breast normal fibroblasts and CAFs of oestrogen receptor-positive cancers, and explore the influences of one of these, miR-26b, on breast cancer biology. We identified differentially expressed microRNAs by expression profiling of clinical samples and a tissue culture model: miR-26b was the most highly deregulated microRNA.

Epithelial-mesenchymal interactions in breast cancer: evidence for a role of nuclear localized β-catenin in carcinoma-associated fibroblasts.

Aims: Characteristics of the stroma around tumours are critical in defining the behaviour of cancers. β-Catenin is well established as a critical regulator of carcinogenesis, acting as a transcriptional co-activator in the nuclei of epithelial cancer cells. We have examined the prevalence and influence of nuclear β-catenin within the stromal fibroblasts of breast cancer.

Phosphorylation of estrogen receptor beta at serine 105 is associated with good prognosis in breast cancer.

Estrogen receptor (ER) action is modulated by posttranslational modifications. Although ERalpha phosphorylation correlates with patient outcome, ERbeta is similarly phosphorylated but its significance in breast cancer has not been addressed. We investigated whether ERbeta that is phosphorylated at serine 105 (S105-ERbeta) is expressed in breast cancer and assessed potential clinical implications of this phosphorylation.

Gene expression of ERbeta isoforms in laser microdissected human breast cancers: implications for gene expression analyses.

Background: Despite many published studies on ERbeta, progress towards understanding its role in breast cancer remains slow. This is largely due to discordant data between mRNA and protein studies as well as failure to take into account the biologically distinct ERbeta isoforms and their heterogeneous expression profile.

Methods: We compared expression of ERbeta1, -2 and -5 genes in HB2 and MCF-7 breast cell lines, primary breast fibroblasts (n=5) and whole tissue and laser microdissected epithelial and stromal cells obtained from 25 human breast tumours.