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Epithelial and Stromal MicroRNA Signatures of Columnar Cell Hyperplasia Linking Let-7c to Precancerous and Cancerous Breast Cancer Cell Proliferation.

Author:
  • Sofie Björner
  • Paul A Fitzpatrick
  • Yaoyong Li
  • Craig Allred
  • Anthony Howell
  • Anita Ringberg
  • Håkan Olsson
  • Crispin J Miller
  • Håkan Axelson
  • Göran Landberg
Publishing year: 2014
Language: English
Publication/Series: PLoS ONE
Volume: 9
Issue: 8
Document type: Journal article
Publisher: Public Library of Science

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • Pathology, Malmö
  • Surgery Research
  • ISSN: 1932-6203
Håkan Axelson
E-mail: hakan.axelson [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 34

MV 404 A31A2

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