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.
Greene
Stephanie B
SB
Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Gunaratne
Preethi H
PH
Hammond
Scott M
SM
Rosen
Jeffrey M
JM
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004847:Epithelial Cells / Q000145:classification / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism*
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse