Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance.
Date
2017-11-30ICR Author
Author
Martin, L-A
Ribas, R
Simigdala, N
Schuster, E
Pancholi, S
Tenev, T
Gellert, P
Buluwela, L
Harrod, A
Thornhill, A
Nikitorowicz-Buniak, J
Bhamra, A
Turgeon, M-O
Poulogiannis, G
Gao, Q
Martins, V
Hills, M
Garcia-Murillas, I
Fribbens, C
Patani, N
Li, Z
Sikora, MJ
Turner, N
Zwart, W
Oesterreich, S
Carroll, J
Ali, S
Dowsett, M
Type
Journal Article
Metadata
Show full item recordAbstract
Resistance to endocrine therapy remains a major clinical problem in breast cancer. Genetic studies highlight the potential role of estrogen receptor-α (ESR1) mutations, which show increased prevalence in the metastatic, endocrine-resistant setting. No naturally occurring ESR1 mutations have been reported in in vitro models of BC either before or after the acquisition of endocrine resistance making functional consequences difficult to study. We report the first discovery of naturally occurring ESR1 Y537C and ESR1 Y537S mutations in MCF7 and SUM44 ESR1-positive cell lines after acquisition of resistance to long-term-estrogen-deprivation (LTED) and subsequent resistance to fulvestrant (ICIR). Mutations were enriched with time, impacted on ESR1 binding to the genome and altered the ESR1 interactome. The results highlight the importance and functional consequence of these mutations and provide an important resource for studying endocrine resistance.
Collections
Subject
Cell Line, Tumor
Humans
Breast Neoplasms
Tamoxifen
Estradiol
Selective Estrogen Receptor Modulators
Estrogen Receptor alpha
Drug Resistance, Neoplasm
Mutation
Female
MCF-7 Cells
Estrogen Receptor Antagonists
Fulvestrant
Research team
Endocrine Therapy Resistance
Molecular Oncology
Signalling & Cancer Metabolism
Endocrinology
Language
eng
Date accepted
2017-10-20
License start date
2017-11-30
Citation
Nature communications, 2017, 8 (1), pp. 1865 - ?
Publisher
NATURE PORTFOLIO