Epithelial and stromal microRNA signatures of columnar cell hyperplasia linking let-7c to precancerous and cancerous breast cancer cell proliferation.
Authors
Björner, SofieFitzpatrick, P
Li, Yaoyong
Allred, C
Howell, Anthony
Ringberg, A
Olsson, H
Miller, Crispin J
Axelson, H
Landberg, Göran
Affiliation
Center for Molecular Pathology, Skåne University Hospital, Department of Laboratory Medicine Malmö, Lund University, Malmö, Sweden; Breakthrough Breast Cancer Research Unit, Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Paterson Institute for Cancer Research, The Christie National Health Service Foundation Trust, Manchester, United Kingdom; Sahlgrenska Cancer Center, Department of Biomedicine, University of Gothenburg, Gothenburg, Sweden.Issue Date
2014
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Show full item recordAbstract
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 α (ERα) 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 post-transcriptional 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. Let-7c were among the identified downregulated epithelial miRNAs and its functions were delineated in unique CCH derived cells and breast cancer cell line MCF-7 suggesting anti-proliferative traits potentially due to effects on Myb and ERα. MiR-132 was upregulated in the stroma surrounding CCH compared to stoma surrounding normal terminal duct lobular units (TDLUs), and overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co-cultured with epithelial CCH cells caused substantial expression changes of genes involved in metabolism, DNA damage and cell motility. The miRNA signatures identified in CCH indicate 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.Citation
Epithelial and stromal microRNA signatures of columnar cell hyperplasia linking Let-7c to precancerous and cancerous breast cancer cell proliferation. 2014, 9 (8):e105099 PLoS ONEJournal
PloS ONEDOI
10.1371/journal.pone.0105099PubMed ID
25122196Type
ArticleLanguage
enISSN
1932-6203ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0105099
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