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Down-regulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells

Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and non-tumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429 and miR-183-96-182...

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Bibliographic Details
Published in:Cell 2009-08, Vol.138 (3), p.592-603
Main Authors: Shimono, Yohei, Ugalde, Maider Zabala, Cho, Robert W., Lobo, Neethan, Dalerba, Piero, Qian, Dalong, Diehn, Maximilian, Liu, Huiping, Panula, Sarita P., Chiao, Eric, Dirbas, Frederick M., Somlo, George, Reijo Pera, Renee A., Lao, Kaiqin, Clarke, Michael F.
Format: Article
Language:English
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Summary:Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and non-tumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429 and miR-183-96-182 were down-regulated in human BCSCs, normal human and murine mammary stem/progenitor cells and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. MiR-200c inhibited the clonogenicity of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro . Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo . The coordinated down-regulation of three microRNA clusters and the similar functional regulation of clonogenicity by miR-200c provide a molecular link that connects breast cancer stem cells with normal stem cells.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2009.07.011