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Breast Cancer Research
Published in: Breast Cancer Research 1/2017

Open Access 01-12-2017 | Research article

Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis

Authors: Igor Bado, Fotis Nikolos, Gayani Rajapaksa, Wanfu Wu, Jessica Castaneda, Savitri Krishnamurthy, Paul Webb, Jan-Åke Gustafsson, Christoforos Thomas

Published in: Breast Cancer Research | Issue 1/2017

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Abstract

Background

Upregulation of estrogen receptor beta (ERβ) in breast cancer cells is associated with epithelial maintenance, decreased proliferation and invasion, and a reduction in the expression of the receptor has been observed in invasive breast tumors. However, proof of an association between loss of ERβ and breast carcinogenesis is still missing.

Methods

To study the role of ERβ in breast oncogenesis, we generated mouse conditional mutants with specific inactivation of ERβ and p53 in the mammary gland epithelium. For epithelium-specific knockout of ERβ and p53, ERβ F/F and p53 F/F mice were crossed to transgenic mice that express the Cre recombinase under the control of the human keratin 14 promoter.

Results

Somatic loss of ERβ significantly accelerated formation of p53-deficient mammary tumors. Loss of the receptor also resulted in the development of less differentiated carcinomas with stronger spindle cell morphology and decreased expression of luminal epithelial markers.

Conclusions

Our results show that synergism between ERβ and p53 inactivation functions to determine important aspects of breast oncogenesis and cancer progression.
Appendix
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Metadata
Title
Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis
Authors
Igor Bado
Fotis Nikolos
Gayani Rajapaksa
Wanfu Wu
Jessica Castaneda
Savitri Krishnamurthy
Paul Webb
Jan-Åke Gustafsson
Christoforos Thomas
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2017
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-017-0872-z

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