The purpose of this up-to-date review is to provide a detailed overview of the specific role of all four Notch receptors (Notch1, Notch2, Notch3, and Notch4) in TNBCs, thus identifying the Notch signaling pathway deregulation/activation as a pathognomonic feature of this breast cancer subtype.
Notch4 was expressed in 55.6% of triple-negative breast cancer (TNBC), 45.8% of Her-2-overexpressing and 25.5% of luminal breast cancer cases, with significantly higher expression occurring in TNBC (P<0.05).
Thus, we establish that BCSC and NOTCH4 activities predict both de novo and acquired tamoxifen resistance and that combining endocrine therapy with targeting JAG1-NOTCH4 overcomes resistance in human breast cancers.
Our finding suggest that targeting Nicastrin and/or Notch4 warrants further clinical evaluation as valid therapeutic strategies in endocrine-resistant breast cancer.
The length of (CA)n in EGFR and (CTG)n in NOTCH4 was not associated with breast cancer (OR=0.99; 95% CI 0.59-1.37; p=0.619 and OR=1.08; 95% CI 0.71-1.65; p=0.725, respectively).
Real-time PCR and Western blot analysis were performed to detect Notch-1, Notch-2, Notch-3 and Notch-4 receptor expression in breast cancer cells when PEA3 was knocked down by siRNA.