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Low Dietary Inorganic Phosphate Stimulates Lung Tumorigenesis Through Altering Protein Translation and Cell Cycle in K-ras(LA1) Mice

Cited 12 time in Web of Science Cited 15 time in Scopus
Authors
Xu, Cheng-Xiong; Jin, Hua; Lim, Hwang-Tae; Ha, Yoon-Cheol; Chae, Chan-Hee; An, Gil-Hwan; Lee, Kee-Ho; Cho, Myung-Haing
Issue Date
2010-04
Citation
Nutrition and Cancer, Vol.62 No.4, pp.525-532
Abstract
Recent surveys indicate that Pi intake has increased steadily as Pi-containing foods have increased. Our previous study demonstrated that high dietary Pi strongly stimulated lung tumorigeneis. In order to answer the issue whether low Pi may be chemopreventive, we examined the effects of low Pi on lung cancer. Eighteen 5-wk-old male K-ras(LA1) lung cancer model mice were randomly allocated to 2 groups. One group was fed a normal diet (0.5% Pi) and other group was fed low Pi (0.1% Pi) diet for 4 wk. Lung cancer development was evaluated by histopathological examination, Western blot, kinase assay, and immunohistochemistry. Low Pi increased the expression of sodium-dependent phosphate cotransporter 2b, and activated Akt signal with decreased PTEN expression in the lungs of K-ras(LA1) mice. Low Pi increased the Akt/mTOR-mediated protein translation through upregulating the phosphorylation of p70S6K and 4E-BP1. In addition, low Pi stimulated cell cycling as evidenced by altered cell cycle regulators such as cyclin D1 and D3. Finally, low Pi increased lung tumorigenesis in K-ras(LA1) mice compared to the normal diet group. Our results clearly demonstrated that low Pi also promoted lung tumorigenesis, thus suggesting that an appropriate intake of dietary Pi may be critical for lung cancer prevention as well as treatment.
ISSN
0163-5581
URI
https://hdl.handle.net/10371/172490
DOI
https://doi.org/10.1080/01635580903532432
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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