Human TaqMan MicroRNA Arrays A and B v2.0 of breast tissue

ABSTRACT: Columnar cell hyperplasia (CCH) is the earliest histologically identifiable breast lesion linked to cancer progression and is characterized by increased proliferation, decreased apoptosis and elevated oestrogen receptor a expression. The mechanisms underlying the initiation of these lesions have not been clarified but might involve early and fundamental changes in cancer progression. MiRNAs are key regulators of several biological processes, acting by influencing the posttranscriptional regulation of numerous targets, thus making miRNAs potential candidates in cancer initiation. Here we have defined novel epithelial as well as stromal miRNA signatures from columnar cell hyperplasia lesions compared to normal terminal duct lobular units by using microdissection and miRNA microarrays. MiR-27a, miR-92a and let-7c were among the identified downregulated epithelial miRNAs and their functions were delineated in unique CCH derived cells suggesting pro-apoptotic and anti-proliferative properties for the selected miRNAs and that downregulation of let-7c in CCH cells potentially increased proliferation via Myb. MiR-132 was upregulated in the stroma surrounding CCH compared to stoma surrounding TDLUs, and overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co-cultured with epithelial CCH cells caused substantial expression changes. Global miRNA expression was also examined both epithelial and stroma of one patient displaying TDLU, CCH and additional invasive breast cancer. The miRNA signatures identified in CCH indicate concordant early changes in the epithelial and stromal compartment of CCH and could represent early key alterations in breast cancer progression that potentially could be targeted in novel prevention or treatment schedules.

ORGANISM(S): Homo sapiens

PROVIDER: GSE46198 | GEO | 2014/07/15

SECONDARY ACCESSION(S): PRJNA198021

REPOSITORIES: GEO