Yes-associated protein promotes tumour development in luminal epithelial derived breast cancer

Eur J Cancer. 2012 May;48(8):1227-34. doi: 10.1016/j.ejca.2011.10.001. Epub 2011 Nov 5.

Abstract

Yes-associated protein (YAP) is inactivated by the tumour suppressing Hippo pathway. The YAP gene is amplified in human liver cancer, and promotes tumour growth. However, there are contrasting reports about its function in breast cancer. Studies have demonstrated both oncogenic or tumour suppressor functions. Our study aims to clarify the role of YAP in breast cancer. We investigated the expression of YAP in 69 cases of human breast cancer tissue by immunohistochemistry (IHC). The role of YAP on cell growth in vitro and tumourigenesis in vivo were evaluated. We found that YAP was expressed in 75.4% (52/69) of breast cancer samples; amongst these cases YAP was overexpressed in 29% (20/69). There was no YAP expression in the remainder (17/69) cases. Breast cancer cell lines in which YAP was either overexpressed or depleted confirmed that YAP markedly promotes cell proliferation. This was confirmed in vivo: overexpression of YAP enhanced tumour formation and growth, whereas downregulation of YAP decreased the tumour formation and growth. Our results suggest that YAP acts as an oncogene in a subtype of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Proteins / analysis
  • Nuclear Proteins / physiology*
  • Phenotype
  • Transcription Factors / analysis
  • Transcription Factors / physiology*

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors
  • YY1AP1 protein, human