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Insufficient antibody validation challenges oestrogen receptor beta research

Andersson, Sandra (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
Sundberg, Mårten (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för kemi - BMC
Pristovsek, Nusa (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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Ibrahim, Ahmed (author)
Karolinska Institutet,KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Sch Biotechnol, Div Prote & Nanotechnol, Sci Life Lab, S-17121 Solna, Sweden.;Natl Res Ctr, Div Pharmaceut Ind, Dokki 12622, Egypt.
Jonsson, Philip (author)
Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
Katona, Borbala (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
Clausson, Carl-Magnus (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
Zieba, Agata (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
Ramström, Margareta (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för kemi - BMC
Söderberg, Ola, 1966- (author)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap
Williams, Cecilia, 1969- (author)
Karolinska Institutet,KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,KTH Royal Inst Technol, Sch Biotechnol, Div Prote & Nanotechnol, Sci Life Lab, S-17121 Solna, Sweden.;Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.;Karolinska Inst, Dept Biosci & Nutr, S-14183 Stockholm, Sweden.
Asplund, Anna (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi
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 (creator_code:org_t)
2017-06-15
2017
English.
In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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  • Journal article (peer-reviewed)
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  • The discovery of oestrogen receptor beta (ER beta/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ER alpha (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-ER beta antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ER beta in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ER beta 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.

Subject headings

TEKNIK OCH TEKNOLOGIER  -- Nanoteknik (hsv//swe)
ENGINEERING AND TECHNOLOGY  -- Nano-technology (hsv//eng)

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