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Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion.
Huang, Tzu-Hsuan; Wu, Fangting; Loeb, Gabriel B; Hsu, Ruby; Heidersbach, Amy; Brincat, Allison; Horiuchi, Dai; Lebbink, Robert J; Mo, Yin-Yuan; Goga, Andrei; McManus, Michael T.
Afiliação
  • Huang TH; Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA.
J Biol Chem ; 284(27): 18515-24, 2009 Jul 03.
Article em En | MEDLINE | ID: mdl-19419954
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Receptor ErbB-2 / Sistema de Sinalização das MAP Quinases / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2009 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Receptor ErbB-2 / Sistema de Sinalização das MAP Quinases / MicroRNAs Tipo de estudo: Prognostic_studies Limite: Female / Humans Idioma: En Ano de publicação: 2009 Tipo de documento: Article