Role of NF-Kappa B Signaling in X-Box Binding Protein 1 (XBP1)-Mediated Antiestrogen Resistance in Breast Cancer
Abstract
Most breast cancer patients who undertake antiestrogen therapy eventually suffers from antiestrogen resistance. Understanding its molecular mechanism is essential for identifying potential targets to overcome antiestrogen resistance. XBP1-S, an important regulator of the unfolded protein response (UPR), is found highly expressed in antiestrogen resistant breast cancer cells and tissues. XBP1-S is believed to function as an important antiestrogen resistance mediator as overexpression of XBP1-S is sufficient to drive resistancy to antiestrogens in MCF7 cells. In this study, we aim to investigate the mechanism of XBP1-mediated antiestorgen resistance, specifically the involvement of NFkappaB signaling. We found that XBP1 regulates NFkappaB signaling at least at two levels. One, XBP1-S regulates RelA expression at the mRNA level; Second, XBP1 regulates NFkappaB transcriptional activity through ERalpha signaling. Furthermore, inhibition of NFkappaB with either Parthenolide (small molecule inhibitor) or p65/RelA knockdown inhibits cell growth and antiestrogen resistance in XBP1-S overexpressed MCF7 cells. Taken together, NFkappaB signaling is required for XBP1-S mediated antiestrogen resistance. Future experiments will be performed in nude mice model to test the role of XBP1-NFkappaB signaling in antiestrogen resistance in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA555915
Entities
People
- Rong Hu
Organizations
- Georgetown University