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

被引：1084

作者：

Shimono, Yohei ^{[1
]}

Zabala, Maider ^{[1
]}

Cho, Robert W. ^{[1
]}

Lobo, Neethan ^{[1
]}

Dalerba, Piero ^{[1
]}

Qian, Dalong ^{[1
]}

Diehn, Maximilian ^{[1
]}

Liu, Huiping ^{[1
]}

Panula, Sarita P. ^{[1
]}

Chiao, Eric ^{[1
]}

Dirbas, Frederick M. ^{[2
]}

Somlo, George ^{[3
]}

Pera, Renee A. Reijo ^{[1
]}

Lao, Kaiqin ^{[4
]}

Clarke, Michael F. ^{[1
]}

机构：

[1] Stanford Univ, Stanford Inst Stem Cell Biol & Regenerat Med, Palo Alto, CA 94304 USA

[2] Stanford Univ, Dept Surg, Stanford, CA 94305 USA

[3] City Hope Canc Ctr, Duarte, CA 91010 USA

[4] Appl Biosyst Inc, Foster City, CA 94404 USA

来源：

CELL | 2009年 / 138卷 / 03期

关键词：

SELF-RENEWAL; MESENCHYMAL TRANSITION; MIR-200; FAMILY; HUMAN TUMORS; EXPRESSION; DICER; IDENTIFICATION; PROLIFERATION; SIGNATURE; MICRORNAS;

D O I：

10.1016/j.cell.2009.07.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-18396-182 were downregulated 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 clonal expansion 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 downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.

引用

收藏

页码：592 / 603

页数：12

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