Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis
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 bet...
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doaj-4e0214d7458b442da0fadf13b89dcd622021-03-02T01:03:25ZengBMCBreast Cancer Research1465-542X2017-07-0119111010.1186/s13058-017-0872-zSomatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesisIgor Bado0Fotis Nikolos1Gayani Rajapaksa2Wanfu Wu3Jessica Castaneda4Savitri Krishnamurthy5Paul Webb6Jan-Åke Gustafsson7Christoforos Thomas8Department of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of HoustonDepartment of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of HoustonDepartment of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of HoustonDepartment of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of HoustonDepartment of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of HoustonDepartment of Pathology, The University of Texas MD Anderson Cancer CenterDepartment of Genomic Medicine, Houston Methodist Research Institute, Houston MethodistDepartment of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of HoustonDepartment of Biology and Biochemistry, Center for Nuclear Receptors and Cell Signaling, University of HoustonAbstract 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.http://link.springer.com/article/10.1186/s13058-017-0872-zEstrogen receptor betaBreast cancerp53Genetically engineered miceBreast carcinogenesis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Igor Bado Fotis Nikolos Gayani Rajapaksa Wanfu Wu Jessica Castaneda Savitri Krishnamurthy Paul Webb Jan-Åke Gustafsson Christoforos Thomas |
spellingShingle |
Igor Bado Fotis Nikolos Gayani Rajapaksa Wanfu Wu Jessica Castaneda Savitri Krishnamurthy Paul Webb Jan-Åke Gustafsson Christoforos Thomas Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis Breast Cancer Research Estrogen receptor beta Breast cancer p53 Genetically engineered mice Breast carcinogenesis |
author_facet |
Igor Bado Fotis Nikolos Gayani Rajapaksa Wanfu Wu Jessica Castaneda Savitri Krishnamurthy Paul Webb Jan-Åke Gustafsson Christoforos Thomas |
author_sort |
Igor Bado |
title |
Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis |
title_short |
Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis |
title_full |
Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis |
title_fullStr |
Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis |
title_full_unstemmed |
Somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis |
title_sort |
somatic loss of estrogen receptor beta and p53 synergize to induce breast tumorigenesis |
publisher |
BMC |
series |
Breast Cancer Research |
issn |
1465-542X |
publishDate |
2017-07-01 |
description |
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. |
topic |
Estrogen receptor beta Breast cancer p53 Genetically engineered mice Breast carcinogenesis |
url |
http://link.springer.com/article/10.1186/s13058-017-0872-z |
work_keys_str_mv |
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