The possible correlation of Notch-1 and Notch-2 with clinical outcome and tumour clinicopathological parameters in human breast cancer

Int J Mol Med. 2004 Nov;14(5):779-86. doi: 10.3892/ijmm.14.5.779.


The Notch-1 and Notch-2 receptors play crucial roles in cell fate determination through interaction with the Delta/Serrate/Lag-2 family of ligands. The function of Notch signalling in tumourigenesis is still unclear, however, reports have demonstrated unregulated Notch activity in a variety of human cancers. We quantified Notch-1 and Notch-2 expression, in association with clinical outcome, in tissue samples from breast cancer patients (normal specimens n=24, breast cancer specimens n=97). We used qualitative and quantitative RT-PCR analysis, along with immunohistochemical staining to examine Notch-1 and Notch-2 expression in association with the patients clinical parameters (median follow-up 72 months). Our results show that there are aberrant levels of Notch-1 and Notch-2 in breast cancer tissues compared with normal breast tissue. Examination of the breast cancer patients' clinicopathological parameters reported that a high level of Notch-1 may be associated with a poorer outlook for the breast cancer patient, while a high level of Notch-2 correlated to a higher chance of survival. Notch-1 and Notch-2 also appear to play crucial and contrasting roles in breast tumour differentiation. Notch-1 expression was low in grade 1 tumours and increased in poorly-differentiated tumours, whereas, Notch-2 expression was high in well-differentiated tumours and reduced in breast tumours with poor differentiation. Therefore, Notch-1 may possess tumour-promoting functions, while Notch-2 could play a tumour-suppressive role in human breast cancer. These results support the notion that suppression of Notch-1 activity may represent a novel therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Breast / cytology
  • Breast / physiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • DNA Primers
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Polymerase Chain Reaction
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptors, Cell Surface / genetics*
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Transcription Factors / genetics*
  • Treatment Outcome


  • DNA Primers
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptors, Cell Surface
  • Transcription Factors