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Phungern Khongthong, Antonia K Roseweir, and Joanne Edwards

). Many comprehensive reviews ( Riggins et al. 2007 , Clarke et al. 2009 , Zhao & Ramaswamy 2014 , Liu et al. 2017 , AlFakeeh & Brezden-Masley 2018 , Masuda et al. 2018 ) summarize the mechanisms of endocrine therapy resistance, including (i

Open access

Jan Kroon, Martin Puhr, Jeroen T Buijs, Geertje van der Horst, Daniëlle M Hemmer, Koen A Marijt, Ming S Hwang, Motasim Masood, Stefan Grimm, Gert Storm, Josbert M Metselaar, Onno C Meijer, Zoran Culig, and Gabri van der Pluijm

the functional involvement of the GR in PCa therapy resistance. Our data fully support this notion and prompted us to further investigate the GR as a therapeutic target in docetaxel-resistant PCa. Our study reveals a strong resensitizing effect to

Free access

K-M Rau, H-Y Kang, T-L Cha, S A Miller, and M-C Hung

elements can promote antihormone-therapy resistance. Membrane ERs can also function like growth factor receptors by binding to p85, a regulatory subunit of phosphoinositide 3-kinase (PI3K) at the cell membrane, leading to activation of the

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Barbara Kuske, Catherine Naughton, Kate Moore, Kenneth G MacLeod, William R Miller, Robert Clarke, Simon P Langdon, and David A Cameron

Hormone-dependent estrogen receptor (ER)-positive breast cancer cells may adapt to low estrogen environments such as produced by aromatase inhibitors. In many instances, cells become insensitive to the effects of estrogen but may still retain dependence on ER. We have investigated the expression, function, and activation of ERα in two endocrine-resistant MCF-7 models to identify mechanisms that could contribute to resistance. While MCF-7/LCC1 cells are partially estrogen dependent, MCF-7/LCC9 cells are fully estrogen insensitive and fulvestrant and tamoxifen resistant. In both MCF-7/LCC1 and MCF-7/LCC9 cell lines, high expression of ERα was associated with enhanced binding to the trefoil factor 1 (TFF1) promoter in the absence of estrogen and increased transcription of TFF1 and progesterone receptor. In contrast to the observations derived from hypersensitive and supersensitive models, these cells were truly estrogen independent; nevertheless, removal of ERα by siRNA, or fulvestrant, a specific ER downregulator, inhibited growth indicating dependence on ERα. In the absence of estrogen, neither ERα Ser118 nor Ser167 were phosphorylated as frequently found in other ligand-independent cell line models. Addition of estrogen activated ERα Ser118 in MCF-7 and LCC1 cells but not in LCC9 cells. We suggest that the estrogen-independent growth within these cell lines is accounted for by high levels of ERα expression driving transcription and full estrogen independence explained by lack of ERα activation through Ser118.

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Eliot B Blatt, Noa Kopplin, Shourya Kumar, Ping Mu, Suzanne D Conzen, and Ganesh V Raj

, darolutamide) and antiestrogens targeting ER (tamoxifen, fulvestrant) have shown efficacy in and improved survival for patients. However, these drugs are rarely curative and endocrine therapy resistance is common, as cancer cells evolve mechanisms to maintain

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Neil Portman, Sarah Alexandrou, Emma Carson, Shudong Wang, Elgene Lim, and C Elizabeth Caldon

those who had received less than 6 months of endocrine therapy. Resistance to CDK4/6 inhibitors is now the major emerging consideration in pre-clinical and clinical drug development. Clinical areas of interest to address resistance include identifying

Open access

Abigail Read and Rachael Natrajan

to increase RNA read lengths, will undoubtedly enhance the ability to detect these events in the future and further increase our understanding of aberrant transcript expression on breast cancer tumourigenesis and therapy resistance. There is

Open access

Martina Gruber, Lavinia Ferrone, Martin Puhr, Frédéric R Santer, Tobias Furlan, Iris E Eder, Natalie Sampson, Georg Schäfer, Florian Handle, and Zoran Culig

AR are involved in therapy resistance with several of them increasingly expressed during ADT ( Comuzzi et al. 2004 , Heemers et al. 2007 , Qin et al. 2014 ). Two of these well-known coactivators are the histone acetyltransferases p300 and CBP

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Isabel Coutinho, Tanya K Day, Wayne D Tilley, and Luke A Selth

(CTCs) and cell-free circulating tumor DNA (ctDNA) from patients with CRPC ( Antonarakis et al . 2014 , Carreira et al . 2014 , Azad et al . 2015 ). Although AR amplification is frequent in CRPC and an important driver of therapy resistance, AR

Free access

Qu Deng and Dean G Tang

. 2005 ). Since 2012 our lab has been employing and developing a variety of experimental strategies to elucidate the cellulose basis and molecular regulation of PCa cell heterogeneity and to link PCa cell heterogeneity to therapy resistance and tumor