Highly Expressed DLL4 and JAG1: Their Role in Incidence of Breast Cancer Metastasis

Arch Med Res. 2020 Feb;51(2):145-152. doi: 10.1016/j.arcmed.2019.12.019. Epub 2020 Feb 26.


Background: The role of Notch signaling dysregulation in causing metastatic breast cancer is not yet elucidated, therefore, this study aimed to investigate the expression of DLL4 and JAG1 in metastatic breast cancer. Moreover, we examined the possible association between clinicopathological features and studied parameters.

Design and methods: A total of 90 patients with invasive ductal breast carcinomas (52 non-metastatic and 38 metastatic) were enrolled in the current study. Furthermore, there were 42 patients with benign breast diseases. The mRNA and protein expression of DLL4 and JAG1 were analyzed by RT-PCR and ELISA, respectively in breast cell lysates.

Results: The mRNA and protein expression of DLL4 and JAG1 were obviously higher in patients with breast cancer compared to patients with benign breast diseases and in metastatic versus non-metastatic breast cancer. A significant positive correlation was declared between DLL4 and JAG1 at both mRNA and protein levels in metastatic and localized breast cancer patients. Highly expressed mRNA and protein of DLL4 and JAG1 were associated with late tumor stages; moreover, upregulation of mRNA and protein of JAG1 was correlated with poorly differentiated tumors.

Conclusion: Our data emphasize that overexpression of DLL4 and JAG1 could predict the development of distant metastasis in breast cancer patients.

Keywords: Breast cancer; Clinicopathological features; DLL4; JAG1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Calcium-Binding Proteins / metabolism*
  • Female
  • Humans
  • Incidence
  • Jagged-1 Protein / genetics
  • Jagged-1 Protein / metabolism*
  • Middle Aged
  • Neoplasm Metastasis / genetics*


  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • DLL4 protein, human
  • JAG1 protein, human
  • Jagged-1 Protein