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Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogen...

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Autores principales: Chen, Jane Q., Mori, Hidetoshi, Cardiff, Robert D., Trott, Josephine F., Hovey, Russell C., Hubbard, Neil E., Engelberg, Jesse A., Tepper, Clifford G., Willis, Brandon J., Khan, Imran H., Ravindran, Resmi K., Chan, Szeman R., Schreiber, Robert D., Borowsky, Alexander D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468083/
https://www.ncbi.nlm.nih.gov/pubmed/26075897
http://dx.doi.org/10.1371/journal.pone.0129895
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author Chen, Jane Q.
Mori, Hidetoshi
Cardiff, Robert D.
Trott, Josephine F.
Hovey, Russell C.
Hubbard, Neil E.
Engelberg, Jesse A.
Tepper, Clifford G.
Willis, Brandon J.
Khan, Imran H.
Ravindran, Resmi K.
Chan, Szeman R.
Schreiber, Robert D.
Borowsky, Alexander D.
author_facet Chen, Jane Q.
Mori, Hidetoshi
Cardiff, Robert D.
Trott, Josephine F.
Hovey, Russell C.
Hubbard, Neil E.
Engelberg, Jesse A.
Tepper, Clifford G.
Willis, Brandon J.
Khan, Imran H.
Ravindran, Resmi K.
Chan, Szeman R.
Schreiber, Robert D.
Borowsky, Alexander D.
author_sort Chen, Jane Q.
collection PubMed
description Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment.
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spelling pubmed-44680832015-06-25 Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent Chen, Jane Q. Mori, Hidetoshi Cardiff, Robert D. Trott, Josephine F. Hovey, Russell C. Hubbard, Neil E. Engelberg, Jesse A. Tepper, Clifford G. Willis, Brandon J. Khan, Imran H. Ravindran, Resmi K. Chan, Szeman R. Schreiber, Robert D. Borowsky, Alexander D. PLoS One Research Article Female 129:Stat1-null mice (129S6/SvEvTac-Stat1(tm1Rds) homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. Public Library of Science 2015-06-15 /pmc/articles/PMC4468083/ /pubmed/26075897 http://dx.doi.org/10.1371/journal.pone.0129895 Text en © 2015 Chen 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
Chen, Jane Q.
Mori, Hidetoshi
Cardiff, Robert D.
Trott, Josephine F.
Hovey, Russell C.
Hubbard, Neil E.
Engelberg, Jesse A.
Tepper, Clifford G.
Willis, Brandon J.
Khan, Imran H.
Ravindran, Resmi K.
Chan, Szeman R.
Schreiber, Robert D.
Borowsky, Alexander D.
Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent
title Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent
title_full Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent
title_fullStr Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent
title_full_unstemmed Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent
title_short Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent
title_sort abnormal mammary development in 129:stat1-null mice is stroma-dependent
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468083/
https://www.ncbi.nlm.nih.gov/pubmed/26075897
http://dx.doi.org/10.1371/journal.pone.0129895
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