Up-regulation of miR-21 by HER2/neu Signaling Promotes Cell Invasion

被引：166

作者：

Huang, Tzu-Hsuan ^{[1
]}

Wu, Fangting ^{[3
]}

Loeb, Gabriel B. ^{[1
]}

Hsu, Ruby ^{[1
]}

Heidersbach, Amy ^{[1
]}

Brincat, Allison ^{[1
]}

Horiuchi, Dai ^{[2
]}

Lebbink, Robert J. ^{[1
]}

Mo, Yin-Yuan ^{[3
]}

Goga, Andrei ^{[2
]}

McManus, Michael T. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Microbiol & Immunol, Div Hematol & Oncol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA 94143 USA

[3] So Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Springfield, IL 62794 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 27期

基金：

美国国家卫生研究院;

关键词：

GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR GENE; BREAST-CANCER; TRANSCRIPTION FACTOR; MICRORNA-21; TARGETS; PROSTATE-CANCER; EXPRESSION; ACTIVATION; OVEREXPRESSION; METASTASIS;

D O I：

10.1074/jbc.M109.006676

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The cell surface receptor tyrosine kinase HER2/neu enhances tumor metastasis. Recent studies suggest that deregulated microRNA (miRNA) expression promotes invasion and metastasis of cancer cells; we therefore explored the possibility that HER2/neu signaling induces the expression of specific miRNAs involved in this process. We identified a putative oncogenic miRNA, miR-21, whose expression is correlated with HER2/neu up-regulation and is functionally involved in HER2/neu-induced cell invasion. We show that miR-21 is up-regulated via the MAPK (ERK1/2) pathway upon stimulation of HER2/neu signaling in breast cancer cells, and overexpression of other ERK1/2 activators such as RASV12 or ID-1 is sufficient to induce miR-21 up-regulation in HER2/neu-negative breast cancer cells. Furthermore, the metastasis suppressor protein PDCD4(programmed cell death 4) is down-regulated by miR-21 in breast cancer cells expressing HER2/neu. Our data reveal a mechanism for HER2/neu-induced cancer cell invasion via miRNA deregulation. In addition, our results identify miR-21 as a potential therapeutic target for the prevention of breast cancer invasion and metastasis.

引用

页码：18515 / 18524

页数：10

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