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Nat Commun. 2017 Jun 15;8:15840. doi: 10.1038/ncomms15840.

Insufficient antibody validation challenges oestrogen receptor beta research.

Author information

1
Department of Immunology, Genetics and Pathology, Uppsala University, Science for Life Laboratory, 751 85 Uppsala, Sweden.
2
Department of Chemistry, Uppsala University, Science for Life Laboratory, 75123 Uppsala, Sweden.
3
Division of Proteomics and Nanotechnology, School of Biotechnology, Science for Life Laboratory, KTH Royal Institute of Technology, 171 21 Solna, Sweden.
4
Division of Pharmaceutical Industries, National Research Centre, Dokki 12622, Egypt.
5
Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204, USA.
6
Department of Pharmaceutical Biosciences, Uppsala University, 75124 Uppsala, Sweden.
7
Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Stockholm, Sweden.

Abstract

The discovery of oestrogen receptor β (ERβ/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ERα (ESR1) raised hopes for improved endocrine therapies. After 20 years of intense research, this has not materialized. We here perform a rigorous validation of 13 anti-ERβ antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ERβ in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ERβ protein in testis, ovary, lymphoid cells, granulosa cell tumours, and a subset of malignant melanoma and thyroid cancers. We do not find evidence of expression in normal or cancerous human breast. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. Our study highlights how inadequately validated antibodies can lead an exciting field astray.

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