MicroRNA-205 regulates HER3 in human breast cancer

Marilena V. Iorio, Patrizia Casalini, Claudia Piovan, Gianpiero Di Leva, Andrea Merlo, Tiziana Triulzi, Sylvie Ménard, Carlo M. Croce, Elda Tagliabue

Research output: Contribution to journalArticlepeer-review

Abstract

An increasing amount of experimental evidence shows that microBNAs can have a causal role in breast cancer tumori- genesis as a novel class of oncogenes or tumor suppressor genes, depending on the targets they regulate. HER2 over- expression is a hallmark of a particularly aggressive subset of breast tumors, and its activation is strictly dependent on the trans-interaction with other members of HER family; in particular, the activation of the PI3K/Akt survival pathway, so critically important in tumorigenesis, is predominantly driven through phosphorylation of the kinase-inactive member HER3. Here, we show that miR-205, down-modulated in breast tumors compared with normal breast tissue, directly targets HER3 receptor, and inhibits the activation of the downstream mediator Akt. The reintroduction of miR-205 in SKBr3 cells inhibits their clonogenic potential and increases the responsiveness to tyrosine-kinase inhibitors Gefitinib and Lapatinib, abrogating the HER3-mediated resistance and restoring a potent proapoptotic activity. Our data describe miR-205 as a new oncosuppressor gene in breast cancer, able to interfere with the proliferative pathway mediated by HER receptor family. Our study also provides experimental evidence suggesting that miR-205 can improve the responsiveness to specific anticancer therapies.

Original languageEnglish
Pages (from-to)2195-2200
Number of pages6
JournalCancer Research
Volume69
Issue number6
DOIs
Publication statusPublished - Mar 15 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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