PTEN Regulates VEGF, VEGFR1 Expression and Its Clinical Significance in Myeloid Leukemia.

Abstract 1001

Poster Board I-23

Phosphatase and tensin homology deleted on chromosome ten (PTEN) as a novel tumor suppressor gene, plays an important role in regulating proliferation, apoptosis, invasion and migration of many cancer cells. PTEN also modulates angiogenesis mediated by vascular endothelial growth factor (VEGF) via down-regulating the activity of PI3K/Akt pathway in many solid tumors. However, in myeloid leukemia, the effects of PTEN on VEGF and VEGFR1 (FLT1) mediated angiogenesis, migration, invasion of leukemia cells and its clinical significance are still unknown. Therefore, in the present study, we investigated the effect of PTEN on the activity of PI3K/Akt and VEGF/FLT1 pathways. Wild type PTEN gene was transfected into K562 cells, a cell line establish from a chronic myelogenous leukemia in blast crisis, to induce high expression of wild-type PTEN gene and protein by the cells. The correlation between the expression levels of PTEN and VEGF/FLT1 and its clinical significance in myeloid leukemia patients were also observed. We found that the expression reconstitution of wild-type PTEN had significance effect on inhibiting proliferation, migration and invasion ability of K562 cells via down-regulation of Akt phosphorylation and inhibition of VEGF/FLT1 expression. In myeloid leukemia patients, a negative correlation was found between the expression level of PTEN mRNA and that of VEGF and FLT1 mRNA. Low expression of PTEN mRNA and high expression of VEGF and FLT1 mRNA indicated a higher tendency of extramedullary disease in acute myeloid leukemia patients. Taken together, our findings indicated that PTEN could modulate the function of VEGF/VEGFR signaling pathway via down regulating Akt phosphorylation and that PTEN would be a candidate target for the treatment of myeloid leukemia.