Abstract 3614: Antibody validation revises estrogen receptor beta research

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.3614-3614
• Main Authors: Andersson, Sandra, Sundberg, Mårten, Pristovsek, Nusa, Ibrahim, Ahmed, Jonsson, Philip, Katona, Borbala, Clausson, Carl-Magnus, Zieba, Agata, Ramström, Margareta, Söderberg, Ola, Williams, Cecilia, Asplund, Anna
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-3614

The discovery of estrogen receptor β (ERβ/ESR2) in 1996 was a landmark discovery. Its homology with breast cancer pharmacological target and predictive biomarker estrogen receptor α (ERα /ESR1) raised hopes for improved endocrine therapies. However, after twenty years of intense research the therapeutic promises have not materialized. We here perform a rigorous validation of 13 anti-ERβ antibodies, and demonstrate that the vast majority are unspecific. Using well-characterized controls and a panel of validation methods, we conclude that only the rarely used monoclonal antibody PPZ0506 targets ERβ in a specific manner in immunohistochemistry. We applied this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, and found that detection of ERβ protein is limited to testis, ovary, placenta, lymphoid cells, granulosa cell tumors, and a subset of malignant melanoma and thyroid cancers. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. We did not find evidence that normal or cancerous human breast express ERβ protein. Our study highlights how inadequately validated antibodies can lead an exciting and promising field astray. Citation Format: Sandra Andersson, Mårten Sundberg, Nusa Pristovsek, Ahmed Ibrahim, Philip Jonsson, Borbala Katona, Carl-Magnus Clausson, Agata Zieba, Margareta Ramström, Ola Söderberg, Cecilia Williams, Anna Asplund. Antibody validation revises estrogen receptor beta research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3614. doi:10.1158/1538-7445.AM2017-3614