Overexpression of Notch-1 induced tamoxifen resistance through down regulation of ESR1 in positive estrogen receptor breast cancer.

Abstract

e11046 Background: Tamoxifen is one of the most widely used drugs in the treatment of estrogen-receptor positive breast cancer, and acquired resistance to tamoxifen during treatment are largely unknown and recent research showed that lower levels of ESR1 associated with tamoxifen resistance in ER-positive breast tumors, from other hand highly expression of Notch-1 and/or Jagged-1 has negative prognostic significance in breast cancer, in this study we show the cross-talk between Notch and the lower levels of ESR1 estrogen receptor positive breast cancer. Methods: A retrospective study with clinico-pathological analysis of 195 patients had ER-positive breast cancer used tamoxifen as an adjuvant systemic therapy, gene expression profiling of paraffin-embedded tumors for ESR1, Real-time PCR and Western blot analysis were performed to detect Notch-1/Jagged-1. Results: From 195 patients 32% had tamoxifen resistance which related with lower levels of ESR1 expression (P=0.019) and there was, a highly significant association of over expression Notch1 protein with the lower levels of ESR1 (P=0.006). Conclusions: The results from this study demonstrate for the first time that Notch-1 regulate levels of ESR1 in ER-positive breast cancer, and partly responsible for tamoxifen resistance, the Notch signaling pathway may be a potential therapeutic target beside current breast cancer therapy and need further investigation to know the mechanism of this pathway.