Inorganic phosphate (Pi) is an essential nutrient to all living systems.Since phosphate cannot be synthesized, the need for this nutrient is met by ingestion of phosphate in the diet, both naturally and as added phosphate.Recent surveys show that the intake of Pi has increased steadily.In our experiment, five-week-old male K-rasLA1 lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks.Our results showed that 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 (NPT-2b) protein levels in the lungs.High dietary consumption of Pi altered pulmonary Akt activity while decreasing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) as well as Akt binding partner carboxyl-terminal modulator protein (CTMP), resulting in increased cap-dependent protein translation.In addition, high dietary Pi significantly increased cell proliferation in the lungs of K-rasLA1 mice.Our results clearly indicated that high dietary Pi promoted tumorigenesis and activated Akt signaling, thus suggesting that appropriate regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.