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Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1

Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1−/− C57/Bl6 female mice to asses...

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Autores principales: LaRocca, Jessica, Pietruska, Jodie, Hixon, Mary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168520/
https://www.ncbi.nlm.nih.gov/pubmed/21915327
http://dx.doi.org/10.1371/journal.pone.0024432
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author LaRocca, Jessica
Pietruska, Jodie
Hixon, Mary
author_facet LaRocca, Jessica
Pietruska, Jodie
Hixon, Mary
author_sort LaRocca, Jessica
collection PubMed
description Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1−/− C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that persist into adulthood. Akt1 deficiency resulted in several mammary gland developmental defects, including ductal outgrowth and defective terminal end bud formation. Adult Akt1−/− mammary gland composition remained altered, exhibiting fewer alveolar buds coupled with increased epithelial cell apoptosis. Microarray analysis revealed that Akt1 deficiency altered expression of genes involved in numerous biological processes in the mammary gland, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1−/− mammary glands. Additionally, pseudopregnant Akt1−/− females failed to induce Btn1a1 expression in response to hormonal stimulation compared to their wild-type counterparts. Retroviral-mediated shRNA knockdown of Akt1 and Btn1a1 in MCF-7 human breast epithelial further illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ß-casein, a gene that encodes for milk protein. Overall these findings provide mechanistic insight into the role of Akt1 in mammary morphogenesis and function.
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spelling pubmed-31685202011-09-13 Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1 LaRocca, Jessica Pietruska, Jodie Hixon, Mary PLoS One Research Article Akt1, a serine-threonine protein kinase member of the PKB/Akt gene family, plays critical roles in the regulation of multiple cellular processes, and has previously been implicated in lactation and breast cancer development. In this study, we utilized Akt1+/+ and Akt1−/− C57/Bl6 female mice to assess the role that Akt1 plays in normal mammary gland postnatal development and function. We examined postnatal morphology at multiple time points, and analyzed gene and protein expression changes that persist into adulthood. Akt1 deficiency resulted in several mammary gland developmental defects, including ductal outgrowth and defective terminal end bud formation. Adult Akt1−/− mammary gland composition remained altered, exhibiting fewer alveolar buds coupled with increased epithelial cell apoptosis. Microarray analysis revealed that Akt1 deficiency altered expression of genes involved in numerous biological processes in the mammary gland, including organismal development, cell death, and tissue morphology. Of particular importance, a significant decrease in expression of Btn1a1, a gene involved in milk lipid secretion, was observed in Akt1−/− mammary glands. Additionally, pseudopregnant Akt1−/− females failed to induce Btn1a1 expression in response to hormonal stimulation compared to their wild-type counterparts. Retroviral-mediated shRNA knockdown of Akt1 and Btn1a1 in MCF-7 human breast epithelial further illustrated the importance of Akt1 in mammary epithelial cell proliferation, as well as in the regulation of Btn1a1 and subsequent expression of ß-casein, a gene that encodes for milk protein. Overall these findings provide mechanistic insight into the role of Akt1 in mammary morphogenesis and function. Public Library of Science 2011-09-07 /pmc/articles/PMC3168520/ /pubmed/21915327 http://dx.doi.org/10.1371/journal.pone.0024432 Text en LaRocca et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
LaRocca, Jessica
Pietruska, Jodie
Hixon, Mary
Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1
title Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1
title_full Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1
title_fullStr Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1
title_full_unstemmed Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1
title_short Akt1 Is Essential for Postnatal Mammary Gland Development, Function, and the Expression of Btn1a1
title_sort akt1 is essential for postnatal mammary gland development, function, and the expression of btn1a1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168520/
https://www.ncbi.nlm.nih.gov/pubmed/21915327
http://dx.doi.org/10.1371/journal.pone.0024432
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