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A putative role for microRNA-205 in mammary epithelial cell progenitors.

In an effort to understand the potential role of microRNAs (miRNAs) in mammary-gland stem or progenitor cells, miRNA microarrays were performed on subpopulations of the mouse mammary epithelial cell (MEC) line COMMA-DbetaGeo. This cell line contains a heterogeneous subpopulation of progenitors characterized by the expression of stem cell antigen 1 (Sca-1; encoded by Ly6a). Microarray analysis indicated that the Sca-1 subpopulations have distinct miRNA expression profiles. Functional studies were performed on miR-205, which was highly expressed in the Sca-1-positive (Sca-1(+)) cells. When miR-205 was overexpressed in vitro, the COMMA-DbetaGeo cells underwent several significant morphological and molecular changes. miR-205 overexpression led to an expansion of the progenitor-cell population, decreased cell size and increased cellular proliferation. In addition, the colony-forming potential of the two Sca-1 subpopulations was increased. Target prediction for miR-205 indicated that it might regulate the expression of the tumor-suppressor protein PTEN. Overexpression studies using reporter constructs confirmed that PTEN expression is regulated by miR-205. In addition to PTEN, several other putative and previously validated miR-205 targets were identified by microarray analysis, including the previously reported miR-205 targets ZEB1 and ZEB2. Additionally, in normal mouse MECs, high expression of miR-205 was observed in stem-cell-enriched cell populations isolated by FACS using established cell-surface markers.

Pubmed ID: 20103531

Authors

  • Greene SB
  • Gunaratne PH
  • Hammond SM
  • Rosen JM

Journal

Journal of cell science

Publication Data

February 15, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: R37 CA016303
  • Agency: NCI NIH HHS, Id: R37-CA16303-33

Mesh Terms

  • Animals
  • Antigens, Ly
  • Base Sequence
  • Cell Differentiation
  • Cell Proliferation
  • Cell Size
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Epithelial Cells
  • Female
  • Gene Expression Profiling
  • Mammary Glands, Animal
  • Membrane Proteins
  • Mice
  • MicroRNAs
  • Oligonucleotide Array Sequence Analysis
  • PTEN Phosphohydrolase
  • Stem Cells