PTEN Loss promotes MAPK pathway dependency in HER2/neu breast carcinomas Academic Article uri icon


MeSH Major

  • MAP Kinase Signaling System
  • Mammary Neoplasms, Experimental
  • Neoplasm Proteins
  • PTEN Phosphohydrolase
  • Receptor, ErbB-2


  • Loss of the tumor suppressor gene PTEN is implicated in breast cancer progression and resistance to targeted therapies, and is thought to promote tumorigenesis by activating PI3K signaling. In a transgenic model of breast cancer, Pten suppression using a tetracycline-regulatable short hairpin (sh)RNA cooperates with human epidermal growth factor receptor 2 (HER2/neu), leading to aggressive and metastatic disease with elevated signaling through PI3K and, surprisingly, the mitogen-activated protein kinase (MAPK) pathway. Restoring Pten function is sufficient to down-regulate both PI3K and MAPK signaling and triggers dramatic tumor regression. Pharmacologic inhibition of MAPK signaling produces similar effects to Pten restoration, suggesting that the MAPK pathway contributes to the maintenance of advanced breast cancers harboring Pten loss.

publication date

  • March 15, 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC4801318

Digital Object Identifier (DOI)

  • 10.1073/pnas.1523693113

PubMed ID

  • 26929372

Additional Document Info


  • 113


  • 11