The human papillomavirus (HPV) 16 E6 oncoprotein leads to an increase in gene expression of the angiogenic switch molecule FGF-BP in non-immortalizedhuman keratinocytes

Fibroblast growth, factor binding protein (FGF-BP) is a secreted protein th at binds, FGF-1 and FGF-2 and is involved in mobilization and activation of FGFs from the extracellular matrix. FGF-BP overexpression as, well as ribo zyme-mediated reduction of endogenous FGF-BP revealed that FGF-BP can be ra te-limiting for tumor growth and angiogenesis. Recent studies showed that F GF-BP expression is up-regulated during early phases of tumorigenesis, indi cating that the role of FGF-BP in angiogenesis is a critical early step in the development and progression of tumors.. Human papillomavirus type, 16 ( HPV 16) is highly associated with the development of anogenital cancers. He re we demonstrate that the stable expression of the E6 oncogene of HPV 16 l eads to an activation of the FGF-BP promoter in primary human foreskin kera tinocytes (one of the natural host cells of these viruses). This is associa ted with, an increase in the steady state levels, of FGF-BP mRNA and FGF-BP protein in cells stably expressing E6. Transient E6 expression revealed th at the observed activation of the FGF-BP promoter by the viral oncogene is, an early process which is. independent from immortalization/transformation , events in the cells.