author_facet Li, Wenmei
Qiao, Wenhui
Chen, Lin
Xu, Xiaoling
Yang, Xiao
Li, Dan
Li, Cuiling
Brodie, Steven G.
Meguid, Michael M.
Hennighausen, Lothar
Deng, Chu-Xia
Li, Wenmei
Qiao, Wenhui
Chen, Lin
Xu, Xiaoling
Yang, Xiao
Li, Dan
Li, Cuiling
Brodie, Steven G.
Meguid, Michael M.
Hennighausen, Lothar
Deng, Chu-Xia
author Li, Wenmei
Qiao, Wenhui
Chen, Lin
Xu, Xiaoling
Yang, Xiao
Li, Dan
Li, Cuiling
Brodie, Steven G.
Meguid, Michael M.
Hennighausen, Lothar
Deng, Chu-Xia
spellingShingle Li, Wenmei
Qiao, Wenhui
Chen, Lin
Xu, Xiaoling
Yang, Xiao
Li, Dan
Li, Cuiling
Brodie, Steven G.
Meguid, Michael M.
Hennighausen, Lothar
Deng, Chu-Xia
Development
Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
Developmental Biology
Molecular Biology
author_sort li, wenmei
spelling Li, Wenmei Qiao, Wenhui Chen, Lin Xu, Xiaoling Yang, Xiao Li, Dan Li, Cuiling Brodie, Steven G. Meguid, Michael M. Hennighausen, Lothar Deng, Chu-Xia 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.00820 <jats:p>Smad4 is a central mediator for TGFβ signals, which play important functions in many biological processes. To study the role of Smad4 in mammary gland development and neoplasia, we disrupted this gene in mammary epithelium using a Cre-loxP approach. Smad4 is expressed in the mammary gland throughout development; however, its inactivation did not cause abnormal development of the gland during the first three pregnancies. Instead, lack of Smad4 gradually induced cell proliferation, alveolar hyperplasia and transdifferentiation of mammary epithelial cells into squamous epithelial cells. Consequently, all mutant mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16 months of age. We demonstrated that absence of Smad4 resulted in β-catenin accumulation at onset and throughout the process of transdifferentiation, implicating β-catenin, a key component of the Wnt signaling pathway, in the development of squamous metaplasia in Smad4-null mammary glands. We further demonstrated that TGFβ1 treatment degraded β-catenin and induced epithelial-mesenchymal transformation in cultured mammary epithelial cells. However, such actions were blocked in the absence of Smad4. These findings indicate that TGFβ/Smad4 signals play a role in cell fate maintenance during mammary gland development and neoplasia.</jats:p> Squamous cell carcinoma and mammary abscess formation through squamous metaplasia in<i>Smad4/Dpc4</i>conditional knockout mice Development
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title Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_unstemmed Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_full Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_fullStr Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_full_unstemmed Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_short Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_sort squamous cell carcinoma and mammary abscess formation through squamous metaplasia in<i>smad4/dpc4</i>conditional knockout mice
topic Developmental Biology
Molecular Biology
url http://dx.doi.org/10.1242/dev.00820
publishDate 2003
physical 6143-6153
description <jats:p>Smad4 is a central mediator for TGFβ signals, which play important functions in many biological processes. To study the role of Smad4 in mammary gland development and neoplasia, we disrupted this gene in mammary epithelium using a Cre-loxP approach. Smad4 is expressed in the mammary gland throughout development; however, its inactivation did not cause abnormal development of the gland during the first three pregnancies. Instead, lack of Smad4 gradually induced cell proliferation, alveolar hyperplasia and transdifferentiation of mammary epithelial cells into squamous epithelial cells. Consequently, all mutant mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16 months of age. We demonstrated that absence of Smad4 resulted in β-catenin accumulation at onset and throughout the process of transdifferentiation, implicating β-catenin, a key component of the Wnt signaling pathway, in the development of squamous metaplasia in Smad4-null mammary glands. We further demonstrated that TGFβ1 treatment degraded β-catenin and induced epithelial-mesenchymal transformation in cultured mammary epithelial cells. However, such actions were blocked in the absence of Smad4. These findings indicate that TGFβ/Smad4 signals play a role in cell fate maintenance during mammary gland development and neoplasia.</jats:p>
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author Li, Wenmei, Qiao, Wenhui, Chen, Lin, Xu, Xiaoling, Yang, Xiao, Li, Dan, Li, Cuiling, Brodie, Steven G., Meguid, Michael M., Hennighausen, Lothar, Deng, Chu-Xia
author_facet Li, Wenmei, Qiao, Wenhui, Chen, Lin, Xu, Xiaoling, Yang, Xiao, Li, Dan, Li, Cuiling, Brodie, Steven G., Meguid, Michael M., Hennighausen, Lothar, Deng, Chu-Xia, Li, Wenmei, Qiao, Wenhui, Chen, Lin, Xu, Xiaoling, Yang, Xiao, Li, Dan, Li, Cuiling, Brodie, Steven G., Meguid, Michael M., Hennighausen, Lothar, Deng, Chu-Xia
author_sort li, wenmei
container_issue 24
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container_title Development
container_volume 130
description <jats:p>Smad4 is a central mediator for TGFβ signals, which play important functions in many biological processes. To study the role of Smad4 in mammary gland development and neoplasia, we disrupted this gene in mammary epithelium using a Cre-loxP approach. Smad4 is expressed in the mammary gland throughout development; however, its inactivation did not cause abnormal development of the gland during the first three pregnancies. Instead, lack of Smad4 gradually induced cell proliferation, alveolar hyperplasia and transdifferentiation of mammary epithelial cells into squamous epithelial cells. Consequently, all mutant mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16 months of age. We demonstrated that absence of Smad4 resulted in β-catenin accumulation at onset and throughout the process of transdifferentiation, implicating β-catenin, a key component of the Wnt signaling pathway, in the development of squamous metaplasia in Smad4-null mammary glands. We further demonstrated that TGFβ1 treatment degraded β-catenin and induced epithelial-mesenchymal transformation in cultured mammary epithelial cells. However, such actions were blocked in the absence of Smad4. These findings indicate that TGFβ/Smad4 signals play a role in cell fate maintenance during mammary gland development and neoplasia.</jats:p>
doi_str_mv 10.1242/dev.00820
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spelling Li, Wenmei Qiao, Wenhui Chen, Lin Xu, Xiaoling Yang, Xiao Li, Dan Li, Cuiling Brodie, Steven G. Meguid, Michael M. Hennighausen, Lothar Deng, Chu-Xia 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.00820 <jats:p>Smad4 is a central mediator for TGFβ signals, which play important functions in many biological processes. To study the role of Smad4 in mammary gland development and neoplasia, we disrupted this gene in mammary epithelium using a Cre-loxP approach. Smad4 is expressed in the mammary gland throughout development; however, its inactivation did not cause abnormal development of the gland during the first three pregnancies. Instead, lack of Smad4 gradually induced cell proliferation, alveolar hyperplasia and transdifferentiation of mammary epithelial cells into squamous epithelial cells. Consequently, all mutant mice developed squamous cell carcinoma and/or mammary abscesses between 5 and 16 months of age. We demonstrated that absence of Smad4 resulted in β-catenin accumulation at onset and throughout the process of transdifferentiation, implicating β-catenin, a key component of the Wnt signaling pathway, in the development of squamous metaplasia in Smad4-null mammary glands. We further demonstrated that TGFβ1 treatment degraded β-catenin and induced epithelial-mesenchymal transformation in cultured mammary epithelial cells. However, such actions were blocked in the absence of Smad4. These findings indicate that TGFβ/Smad4 signals play a role in cell fate maintenance during mammary gland development and neoplasia.</jats:p> Squamous cell carcinoma and mammary abscess formation through squamous metaplasia in<i>Smad4/Dpc4</i>conditional knockout mice Development
spellingShingle Li, Wenmei, Qiao, Wenhui, Chen, Lin, Xu, Xiaoling, Yang, Xiao, Li, Dan, Li, Cuiling, Brodie, Steven G., Meguid, Michael M., Hennighausen, Lothar, Deng, Chu-Xia, Development, Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice, Developmental Biology, Molecular Biology
title Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_full Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_fullStr Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_full_unstemmed Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_short Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
title_sort squamous cell carcinoma and mammary abscess formation through squamous metaplasia in<i>smad4/dpc4</i>conditional knockout mice
title_unstemmed Squamous cell carcinoma and mammary abscess formation through squamous metaplasia inSmad4/Dpc4conditional knockout mice
topic Developmental Biology, Molecular Biology
url http://dx.doi.org/10.1242/dev.00820