[Exploration of the Role of Tumor Suppressor Genes Foxo1 and PTEN in the Tumorigenesis of Mouse Natural Killer-Cell Lymphoma]

Objective: To explore whether tumor suppressor gene Foxo1 and PTEN play a critical role in the tumorigenesis of mouse natural killer-cell lymphoma.

Methods: NKp46-iCre mice were crossed with mice carrying floxed Foxo1 alleles (Foxo1^fl/fl) as well as floxed PTEN alleles (PTEN^fl/fl) to generate mice in which Foxo1 and PTEN in NK cells were knock-out, referred as Foxo1^△NKPTEN^△NK. The growth and development of the mice and tumor formation were observed. The flow cytometry was used to detect the percentages of NK cells in main lymphatic organs. B16F10 metanoma model of tumor metastasis was utilized to investigate NK cell-mediated tumor surveillance in vivo after NK cells special deletion of Foxol and PTEN.

Results: The mouse model with NK cell-special Foxo1 and PTEN double knockout was established. Compared with control group (Foxo1^fl/flPTEN^fl/fl mice), Foxo1^△NKPTEN^△NK mice were born alive and appeared to be healthy over a period of 46 weeks. No spontaneous tumor formation was observed at this stage. There were no significant differences in NK cell percentages of gated lymphocytes from various organs including blood, bone marrow, peripheral lymph node and spleen between Foxo1^△NKPTEN^△NK mice and Foxo1^fl/flPTEN^fl/fl mice [PB: 4.76%±0.46% vs 4.17%±0.64% (P＞0.05, n=8); BM: 1.13%±0.23% vs 1.31%±0.10% (P＞0.05, n=8) ; LN: 0.50%±0.10% vs 0.85%±0.20% (P＞0.05, n=8); SP: 4.41%±0.65% vs 3.50%±0.24% (P＞0.05, n=8)]. B16F10 melanoma metastasis model of tumor was established, No differences in median survival time were observed in the 2 types of mice (P＞0.05, n=13).

Conclusion: The simultaneous deletion of the Foxo1 and PTEN genes may not plays significant role in the tumorigenesis of mouse natural killer-cell lymphoma and NK cell-mediated tumor surveillance in vivo.