@article{Volpato2020,
abstract = {Aim: Tamoxifen (TAM) resistance remains a clinical issue in breast cancer. The authors previously reported that 15-hydroxyprostaglandin dehydrogenase (HPGD) was significantly downregulated in tamoxifen-resistant (TAMr) breast cancer cell lines. Here, the authors investigated the relationship between HPGD expression, TAM resistance and prediction of outcome in breast cancer. Methods: HPGD overexpression and silencing studies were performed in isogenic TAMr and parental human breast cancer cell lines to establish the impact of HPGD expression on TAM resistance. HPGD expression and clinical outcome relationships were explored using immunohistochemistry and in silico analysis. Results: Restoration of HPGD expression and activity sensitised TAMr MCF-7 cells to TAM and 17$\beta$-oestradiol, whilst HPGD silencing in parental MCF-7 cells reduced TAM sensitivity. TAMr cells released more prostaglandin E2 (PGE2) than controls, which was reduced in TAMr cells stably transfected with HPGD. Exogenous PGE2 signalled through the EP4 receptor to reduce breast cancer cell sensitivity to TAM. Decreased HPGD expression was associated with decreased overall survival in ER$\alpha$-positive breast cancer patients. Conclusions: HPGD downregulation in breast cancer is associated with reduced response to TAM therapy via PGE2-EP4 signalling and decreases patient survival. The data offer a potential target to develop combination therapies that may overcome acquired tamoxifen resistance.},
author = {Volpato, Milene and Cummings, Michele and Shaaban, Abeer M and Abderrahman, Balkees and Hull, Mark A and Maximov, Philipp Y and Broom, Bradley M and Hoppe, Reiner and Fan, Ping and Brauch, Hiltrud and Jordan, V Craig and Speirs, Valerie},
doi = {10.37349/etat.2020.00021},
journal = {Exploration of Targeted Anti-tumor Therapy},
keywords = {15-hydroxyprostaglandin dehydrogenase,breast cancer,endocrine resistance,immunohistochemistry,survival},
number = {5},
pages = {355--371},
title = {{Downregulation of 15-hydroxyprostaglandin dehydrogenase during acquired tamoxifen resistance and association with poor prognosis in ER$\alpha$-positive breast cancer}},
url = {https://www.explorationpub.com/Journals/etat/Article/100221},
volume = {1},
year = {2020}
}