Serum stimulates Pleiotrophin gene expression in an AP-1-dependent manner in human endothelial and glioblastoma cells.

Despite the fact that pleiotrophin (PTN) exhibits important biological activities related to tumor growth and angiogenesis, little is known about the regulation of its expression. In the present work, the effect of serum on PTN expression and secretion in the culture medium of human umbilical vein endothelial (HUVECs) and glioblastoma M059K cells was studied. The protein levels of PTN were estimated by Western blot and pin transcription was estimated by measuring luciferase activity of a reporter gene vector carrying the wild-type or mutated full length promoter of the ptn gene. Serum induced PTN protein secretion in both types of cells and up-regulated luciferase activity of the ptn promoter in a time- and concentration-dependent manner. Use of a mutant construct that lacked the serum response element (SRE) showed that serum-induced luciferase activity was partially abolished in HUVECs but not affected in M059K cells. Transfection with a construct mutated at both AP-1 binding sites led to complete abolishment of the serum-induced ptn transcription in both types of cells. The two AP-1 binding sites of the ptn promoter are involved in the serum stimulation of its expression, while SRE involvement seems to be partial and cell type-specific.