High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling.
BACKGROUND
Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis.


OBJECTIVE
The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development.


METHODS
Experiments were performed on 5-week-old male K-ras(LA1) lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice. Mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks. At the end of the experiment, all mice were killed. Lung cancer development was evaluated by diverse methods.


RESULTS
A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter-2b protein levels in the lungs. High dietary consumption of Pi stimulated pulmonary Akt activity while suppressing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 as well as Akt binding partner carboxyl-terminal modulator protein, resulting in facilitated cap-dependent protein translation. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-ras(LA1) mice.


CONCLUSIONS
Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.
Jin
Hua
H
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Xu
Cheng-Xiong
CX
Lim
Hwang-Tae
HT
Park
Sung-Jin
SJ
Shin
Ji-Young
JY
Chung
Youn-Sun
YS
Park
Se-Chang
SC
Chang
Seung-Hee
SH
Youn
Hee-Jeong
HJ
Lee
Kee-Ho
KH
Lee
Yeon-Sook
YS
Ha
Yoon-Cheol
YC
Chae
Chan-Hee
CH
Beck
George R
GR
Cho
Myung-Haing
MH
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism; D004032:Diet; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000628:therapy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010170:Palmitoyl-CoA Hydrolase; D016226:Phosphorus, Dietary / Q000008:administration & dosage*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D002352:Carrier Proteins; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D016226:Phosphorus, Dietary; D018809:Proliferating Cell Nuclear Antigen; D051057:Proto-Oncogene Proteins c-akt; C527670:CTMP protein, mouse; D010170:Palmitoyl-CoA Hydrolase; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse