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The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ

The key molecular events required for the formation of Ductal Carcinoma in Situ (DCIS) and its progression to invasive breast carcinoma have not been defined. Here we show that the nuclear receptor coactivator Amplified In Breast cancer 1 (AIB1) is expressed at low levels in normal breast but is hig...

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Autores principales: Ory, V, Tassi, E, Cavalli, LR, Sharif, GM, Saenz, F, Baker, T, Schmidt, MO, Mueller, SC, Furth, PA, Wellstein, A, Riegel, AT
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943533/
https://www.ncbi.nlm.nih.gov/pubmed/23851504
http://dx.doi.org/10.1038/onc.2013.263
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author Ory, V
Tassi, E
Cavalli, LR
Sharif, GM
Saenz, F
Baker, T
Schmidt, MO
Mueller, SC
Furth, PA
Wellstein, A
Riegel, AT
author_facet Ory, V
Tassi, E
Cavalli, LR
Sharif, GM
Saenz, F
Baker, T
Schmidt, MO
Mueller, SC
Furth, PA
Wellstein, A
Riegel, AT
author_sort Ory, V
collection PubMed
description The key molecular events required for the formation of Ductal Carcinoma in Situ (DCIS) and its progression to invasive breast carcinoma have not been defined. Here we show that the nuclear receptor coactivator Amplified In Breast cancer 1 (AIB1) is expressed at low levels in normal breast but is highly expressed in DCIS lesions. This is of significance since reduction of AIB1 in human MCFDCIS cells restored a more normal 3D mammary acinar structure. Reduction of AIB1 in MCFDCIS cells, both prior to DCIS development or in existing MCFDCIS lesions in vivo, inhibited tumor growth and led to smaller, necrotic lesions. AIB1 reduction in MCFDCIS cells was correlated with significant reduction in the CD24−/CD44+ Breast Cancer Initiating Cells (BCIC) population, and a decrease in myoepithelial progenitor cells in the DCIS lesions in vitro and in vivo. Loss of AIB1 in MCFDCIS cells was also accompanied by a loss of expression of NOTCH 2, 3 and 4, JAG2, HES1, GATA3, HER2 and HER3 in vivo. These signaling molecules have been associated with differentiation of breast epithelial progenitor cells. These data indicate that AIB1 plays a central role in the initiation and maintenance of DCIS and that reduction of AIB1 causes loss of BCIC, loss of components of the NOTCH, HER2 and HER3 signaling pathways and fewer DCIS myoepithelial progenitor cells in vivo. We propose that increased expression of AIB1, through maintenance of BCIC, facilitates formation of DCIS, a necessary step prior to development of invasive disease.
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spelling pubmed-39435332014-12-05 The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ Ory, V Tassi, E Cavalli, LR Sharif, GM Saenz, F Baker, T Schmidt, MO Mueller, SC Furth, PA Wellstein, A Riegel, AT Oncogene Article The key molecular events required for the formation of Ductal Carcinoma in Situ (DCIS) and its progression to invasive breast carcinoma have not been defined. Here we show that the nuclear receptor coactivator Amplified In Breast cancer 1 (AIB1) is expressed at low levels in normal breast but is highly expressed in DCIS lesions. This is of significance since reduction of AIB1 in human MCFDCIS cells restored a more normal 3D mammary acinar structure. Reduction of AIB1 in MCFDCIS cells, both prior to DCIS development or in existing MCFDCIS lesions in vivo, inhibited tumor growth and led to smaller, necrotic lesions. AIB1 reduction in MCFDCIS cells was correlated with significant reduction in the CD24−/CD44+ Breast Cancer Initiating Cells (BCIC) population, and a decrease in myoepithelial progenitor cells in the DCIS lesions in vitro and in vivo. Loss of AIB1 in MCFDCIS cells was also accompanied by a loss of expression of NOTCH 2, 3 and 4, JAG2, HES1, GATA3, HER2 and HER3 in vivo. These signaling molecules have been associated with differentiation of breast epithelial progenitor cells. These data indicate that AIB1 plays a central role in the initiation and maintenance of DCIS and that reduction of AIB1 causes loss of BCIC, loss of components of the NOTCH, HER2 and HER3 signaling pathways and fewer DCIS myoepithelial progenitor cells in vivo. We propose that increased expression of AIB1, through maintenance of BCIC, facilitates formation of DCIS, a necessary step prior to development of invasive disease. 2013-07-15 2014-06-05 /pmc/articles/PMC3943533/ /pubmed/23851504 http://dx.doi.org/10.1038/onc.2013.263 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ory, V
Tassi, E
Cavalli, LR
Sharif, GM
Saenz, F
Baker, T
Schmidt, MO
Mueller, SC
Furth, PA
Wellstein, A
Riegel, AT
The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ
title The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ
title_full The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ
title_fullStr The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ
title_full_unstemmed The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ
title_short The nuclear coactivator Amplified In Breast Cancer 1 maintains tumor initiating cells during development of Ductal Carcinoma In Situ
title_sort nuclear coactivator amplified in breast cancer 1 maintains tumor initiating cells during development of ductal carcinoma in situ
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943533/
https://www.ncbi.nlm.nih.gov/pubmed/23851504
http://dx.doi.org/10.1038/onc.2013.263
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