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Håkan Axelson

Håkan Axelson

Research team manager

Håkan Axelson

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

Summary, in 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.

Department/s

  • Pathology, Malmö
  • Surgery
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Breastcancer-genetics
  • Division of Translational Cancer Research
  • EpiHealth: Epidemiology for Health

Publishing year

2014

Language

English

Publication/Series

PLoS ONE

Volume

9

Issue

8

Document type

Journal article

Publisher

Public Library of Science (PLoS)

Topic

  • Cancer and Oncology

Status

Published

Research group

  • Pathology, Malmö
  • Surgery

ISBN/ISSN/Other

  • ISSN: 1932-6203