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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4540575?pdf=render |
| _version_ | 1818316348226273280 |
|---|---|
| author | Somin Lee Ji-Eun Kim Seong-Ho Hong Ah-Young Lee Eun-Jung Park Hwi Won Seo Chanhee Chae Philip Doble David Bishop Myung-Haing Cho |
| author_facet | Somin Lee Ji-Eun Kim Seong-Ho Hong Ah-Young Lee Eun-Jung Park Hwi Won Seo Chanhee Chae Philip Doble David Bishop Myung-Haing Cho |
| author_sort | Somin Lee |
| collection | DOAJ |
| 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-rasLA1 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. |
| first_indexed | 2024-12-13T09:20:00Z |
| format | Article |
| id | doaj.art-a0aea08c7b054ce89c8a724046676cf6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:20:00Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a0aea08c7b054ce89c8a724046676cf62022-12-21T23:52:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013558210.1371/journal.pone.0135582High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer.Somin LeeJi-Eun KimSeong-Ho HongAh-Young LeeEun-Jung ParkHwi Won SeoChanhee ChaePhilip DobleDavid BishopMyung-Haing ChoInorganic 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-rasLA1 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.http://europepmc.org/articles/PMC4540575?pdf=render |
| spellingShingle | Somin Lee Ji-Eun Kim Seong-Ho Hong Ah-Young Lee Eun-Jung Park Hwi Won Seo Chanhee Chae Philip Doble David Bishop Myung-Haing Cho High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC4540575?pdf=render |
| work_keys_str_mv | AT sominlee highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT jieunkim highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT seonghohong highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT ahyounglee highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT eunjungpark highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT hwiwonseo highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT chanheechae highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT philipdoble highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT davidbishop highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer AT myunghaingcho highinorganicphosphateintakepromotestumorigenesisatearlystagesinamousemodeloflungcancer |