PO-090 Expression of the cocaine- and amphetamine-regulated transcript (CART) recruits SWI/SNF chromatin remodelling complexes to the oestrogen receptor

Introduction Cocaine- and amphetamine-regulated transcript (CART) peptides are neuropeptides involved in regulating physiological processes, such as feeding and drug reward. Recent studies have associated high CART expression with worse overall survival in patients with small-bowel carcinoid tumours and oestrogen receptor-positive (ER+), lymph node-negative breast cancer. CART was also shown to be associated with poor patient response to tamoxifen, suggesting CART may play a role in conferring tamoxifen resistance. Material and methods We have previously demonstrated that CART can impact the transcriptional activity of ERα through the use of western blotting and qPCR for specific ERα gene targets. RNA sequencing was carried out using a stable CART-inducible cell line model to identify genes which are upregulated/downregulated in cells expressing CART. Further, using our stable CART-inducible cell line model, we preformed ERα-Immunoprecipitation followed by in-solution mass spectrometry to identify differentially recruited protein complexes+/-CART expression. Results and discussions RNA sequencing revealed 156 significantly downregulated, and 100 significantly upregulated, genes in cells expressing CART (p in silico analysis demonstrated high expression of SMARCD1 correlates with poor overall survival (OS) (p Conclusion In conclusion, we suggest that CART expression results in the recruitment of chromatin remodelling complexes to ERα in order to facilitate the regulation of receptor function.