| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that regulate a wide range of cellular processes, among which are cell survival, growth, and proliferation, processes whose misregulation contributes to cancer. There are 4 members in the PI3K class I family, in which the catalytic subunits are p 110α, p 110β, p 110γ, and p 110δ isoforms.
To reveal its role in cancer development, we examined the effect of deleting various isoforms of PI3K (p85α, p 110α, p 110γ, and p 110δ) on epithelial neoplasma in PTEN-/-mice.
Interestingly, we found that either the heterozygous loss of p110α or the homozygous loss of p 110γ led to ecreased incidence of epithelial neoplasma. These results indicate that decreasing the levels of different p 110 subunits can result in decreased PI3K signaling in epidermis, supporting the model that both p110α and p 110γ can function as inhibitors of PI3K signaling in some tissues and thus suppress tumor formation.
Taken together, our results suggest that both the p110α and p 110γ play crucial roles in mediating PI3K signaling in epithelial neoplastic lesions in PTEN-/-mice, and therapeutic approaches that target the PI3K pathway in cancer may exploit such differences between these isoforms.
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