Aberrant expression and clinical correlation of Notch signaling molecules in breast cancer of Chinese population

Abstract

Aims: Notch signaling molecules play crucial roles in cell proliferation and apoptosis, yet their function in breast cancer remains unclear. Methods: Samples and clinical data from 62 breast cancer patients were collected. After total RNA isolation, reverse transcription polymerase chain reaction was applied to analyze the expression of Notch receptors (Notch1, Notch3 and Notch4) and ligands (DLL4 and JAG1), and their clinical association. Immunohistochemical analysis was used to detect the intracellular domain of Notch1 (Notch1-IC) expression. Results: Notch1 was the dominant receptor while DLL4 was the dominant ligand. The Notch molecules expression pattern for infiltrating ductal carcinoma (IDC) was similar to that for infiltrating lobular carcinoma (ILC) except for JAG1, while Notch1 standard coefficients in ILC were statistically higher than that in IDC. Immunohistochemical results showed that Notch1-IC protein expression paralleled the mRNA level. Breast cancer patients' clinical parameters suggested that Notch1 expression was higher in stage II disease and lower in more advanced stages. The Notch3 positive rate was higher in patients with lower levels of Notch1, and the Notch3 positive rate was lower in patients with higher levels of Notch1. No apparent correlation of Notch molecules with estrogen receptor (ER), progesterone receptor (PR) was found. Though high Notch1 and Notch3 RNA levels tended to correlate with c-erbB2 expression, no statistical significance was found. Conclusion: Notch molecules are useful biomarkers in breast cancer especially for Notch1 and DLL4, and Notch1 is expressed differently in different stages of human breast cancer. © 2011 Blackwell Publishing Asia Pty Ltd.