High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer

Inorganic phosphate (Pi) is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lun...

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Autores principales: Lee, Somin, Kim, Ji-Eun, Hong, Seong-Ho, Lee, Ah-Young, Park, Eun-Jung, Seo, Hwi Won, Chae, Chanhee, Doble, Philip, Bishop, David, Cho, Myung-Haing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540575/
https://www.ncbi.nlm.nih.gov/pubmed/26285136
http://dx.doi.org/10.1371/journal.pone.0135582
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author Lee, Somin
Kim, Ji-Eun
Hong, Seong-Ho
Lee, Ah-Young
Park, Eun-Jung
Seo, Hwi Won
Chae, Chanhee
Doble, Philip
Bishop, David
Cho, Myung-Haing
author_facet Lee, Somin
Kim, Ji-Eun
Hong, Seong-Ho
Lee, Ah-Young
Park, Eun-Jung
Seo, Hwi Won
Chae, Chanhee
Doble, Philip
Bishop, David
Cho, Myung-Haing
author_sort Lee, Somin
collection PubMed
description Inorganic phosphate (Pi) is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lung cancer progression. This study investigated the effects of a high-phosphate diet (HPD) in a mouse model of adenocarcinoma. K-ras(LA1) mice were fed a normal diet (0.3% Pi) or an HPD (1% Pi) for 1, 2, or 4 months. Mice were then sacrificed and subjected to inductively coupled plasma mass/optical emission spectrometry and laser ablation inductively coupled plasma mass-spectrometry analyses, western blot analysis, histopathological, immunohistochemical, and immunocytochemical analyses to evaluate tumor formation and progression (including cell proliferation, angiogenesis, and apoptosis), changes in ion levels and metabolism, autophagy, epithelial-to-mesenchymal transition, and protein translation in the lungs. An HPD accelerated tumorigenesis, as evidenced by increased adenoma and adenocarcinoma rates as well as tumor size. However, after 4 months of the HPD, cell proliferation was arrested, and marked increases in liver and lung ion levels and in energy production via the tricarboxylic acid cycle in the liver were observed, which were accompanied by increased autophagy and decreased angiogenesis and apoptosis. These results indicate that an HPD initially promotes but later inhibits lung cancer progression because of metabolic adaptation leading to tumor cell quiescence. Moreover, the results suggest that carefully regulated Pi consumption are effective in lung cancer prevention.
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spelling pubmed-45405752015-08-24 High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer Lee, Somin Kim, Ji-Eun Hong, Seong-Ho Lee, Ah-Young Park, Eun-Jung Seo, Hwi Won Chae, Chanhee Doble, Philip Bishop, David Cho, Myung-Haing PLoS One Research Article Inorganic phosphate (Pi) is required by all living organisms for the development of organs such as bone, muscle, brain, and lungs, regulating the expression of several critical genes as well as signal transduction. However, little is known about the effects of prolonged dietary Pi consumption on lung cancer progression. This study investigated the effects of a high-phosphate diet (HPD) in a mouse model of adenocarcinoma. K-ras(LA1) mice were fed a normal diet (0.3% Pi) or an HPD (1% Pi) for 1, 2, or 4 months. Mice were then sacrificed and subjected to inductively coupled plasma mass/optical emission spectrometry and laser ablation inductively coupled plasma mass-spectrometry analyses, western blot analysis, histopathological, immunohistochemical, and immunocytochemical analyses to evaluate tumor formation and progression (including cell proliferation, angiogenesis, and apoptosis), changes in ion levels and metabolism, autophagy, epithelial-to-mesenchymal transition, and protein translation in the lungs. An HPD accelerated tumorigenesis, as evidenced by increased adenoma and adenocarcinoma rates as well as tumor size. However, after 4 months of the HPD, cell proliferation was arrested, and marked increases in liver and lung ion levels and in energy production via the tricarboxylic acid cycle in the liver were observed, which were accompanied by increased autophagy and decreased angiogenesis and apoptosis. These results indicate that an HPD initially promotes but later inhibits lung cancer progression because of metabolic adaptation leading to tumor cell quiescence. Moreover, the results suggest that carefully regulated Pi consumption are effective in lung cancer prevention. Public Library of Science 2015-08-18 /pmc/articles/PMC4540575/ /pubmed/26285136 http://dx.doi.org/10.1371/journal.pone.0135582 Text en © 2015 Lee 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
Lee, Somin
Kim, Ji-Eun
Hong, Seong-Ho
Lee, Ah-Young
Park, Eun-Jung
Seo, Hwi Won
Chae, Chanhee
Doble, Philip
Bishop, David
Cho, Myung-Haing
High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer
title High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer
title_full High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer
title_fullStr High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer
title_full_unstemmed High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer
title_short High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer
title_sort high inorganic phosphate intake promotes tumorigenesis at early stages in a mouse model of lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540575/
https://www.ncbi.nlm.nih.gov/pubmed/26285136
http://dx.doi.org/10.1371/journal.pone.0135582
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