Primed atypical ductal hyperplasia-associated fibroblasts promote cell growth and polarity changes of transformed epithelium-like breast cancer MCF-7 cells via miR-200b/c-IKKβ signaling

Cell Death Dis. 2018 Jan 26;9(2):122. doi: 10.1038/s41419-017-0133-1.

Abstract

Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating cancer cell proliferation, and invasion, but how the premalignant stromal fibroblasts trigger epithelial changes remain unclear. We demonstrate that atypical ductal hyperplasia-associated fibroblasts (AHFs) are one kind of activated fibroblasts and stimulate cell growth and polarity change of epithelium-like tumor cell MCF-7 as CAFs-like fibroblasts. Microarray shows miR-200b and miR-200c are downregulated during AHFs and CAFs, and contribute to stromal fibroblast activity. Additionally, miR-200b/c with target gene IKKβ (inhibitor of nuclear factor kappa-B kinase β) control PAI-1 (plasminogen activator inhibitor-1) expression to regulate growth and polarity changes of MCF-7 cells through NF-κB pathway. Exploring the difference of AHFs in premalignant transformation is crucial for understanding the pathobiology of breast cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Carcinoma, Intraductal, Noninfiltrating / pathology*
  • Cell Polarity*
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • Epithelium / pathology*
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • I-kappa B Kinase / metabolism*
  • MCF-7 Cells
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Myofibroblasts / pathology
  • NF-kappa B / metabolism
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Signal Transduction*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Plasminogen Activator Inhibitor 1
  • I-kappa B Kinase