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

Hubert Stöppler,Claudius Malerczyk,Achim Aigner,Frank Czubayko,Katrin Block

doi:10.1038/sj.onc.1204957

Hubert Stöppler, Claudius Malerczyk + Show 3 more

Open Access

https://doi.org/10.1038/sj.onc.1204957

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Journal: Oncogene	Publication Date: Nov 1, 2001
Citations: 19	License type: cc-by

Affiliation: Philipps University of Marburg

Abstract

Fibroblast growth factor binding protein (FGF-BP) is a secreted protein that 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 ribozyme-mediated reduction of endogenous FGF-BP revealed that FGF-BP can be rate-limiting for tumor growth and angiogenesis. Recent studies showed that FGF-BP expression is up-regulated during early phases of tumorigenesis, indicating 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. Here we demonstrate that the stable expression of the E6 oncogene of HPV 16 leads to an activation of the FGF-BP promoter in primary human foreskin keratinocytes (one of the natural host cells of these viruses). This is associated 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 that 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.

Highlights

Fibroblast growth factors (FGFs) are a family of 21 heparin-binding polypeptide growth factors that play an important role in embryonic development as well as in tumorigenesis
It has been shown that the binding of FGF to FGF binding protein (FGF-BP) mobilizes FGF-2 from the heparan sulfate proteoglycans of the extracellular matrix, leading to the activation of growth factor activities of FGF-2 (Czubayko et al, 1994, 1997)
An up-regulation of FGF-BP mRNA was found in the early stages of embryonic mouse development and during carcinogen-induced transformation of adult murine skin, which was associated with histological changes that can be characterized as preneoplastic (Kurtz et al, 1997)

Summary

Introduction

Fibroblast growth factors (FGFs) are a family of 21 heparin-binding polypeptide growth factors that play an important role in embryonic development as well as in tumorigenesis. We analysed here whether the HPV oncoproteins E6 or E7 of thehigh risk' HPV type 16 inuence FGF-BP promoter activity in the transition phase between senescent and immortal growth in primary human foreskin keratinocytes, a natural host cell of these viruses.

Results

Conclusion