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

• Published in: Oncogene Vol. 20; no. 50; pp. 7430 - 7436
• Main Authors: STÖPPLER, Hubert, MALERCZYK, Claudius, BLOCK, Katrin, AIGNER, Achim, CZUBAYKO, Frank
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01.11.2001; Nature Publishing Group
• Subjects: AE6 protein; Angiogenesis; Anogenital; Biological and medical sciences; Carcinogens; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Cell Line; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular Senescence; Development and progression; E6 protein; Epidermal growth factor; Extracellular matrix; FGF-BP protein; Fibroblast growth factor 1; Fibroblast growth factor 2; fibroblast growth factor-binding protein; Fibroblast growth factors; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Viral; Genes, Reporter; Genetic research; Heparan sulfate; Human papillomavirus; human papillomavirus 16; Humans; Immortalization; Intercellular Signaling Peptides and Proteins; Keratinocytes; Keratinocytes - cytology; Keratinocytes - metabolism; Kinases; Luciferases - biosynthesis; Male; Messenger RNA; Molecular and cellular biology; Neovascularization, Pathologic - genetics; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - physiology; Oncoproteins; Papillomavirus E7 Proteins; Papillomavirus infections; Papillomaviruses; Penis - cytology; Peptides; Promoter Regions, Genetic; Protein binding; Proteins; Recombinant Fusion Proteins - biosynthesis; Repressor Proteins; RNA, Messenger - biosynthesis; Simian virus 40 - genetics; Transcriptional Activation; Transfection; Tumor Suppressor Protein p53 - biosynthesis; Tumorigenesis; Tumors; Papillomavirus; Virus; Human; Angiogenesis; Human papillomavirus 16; Human papillomavirus; Lead; Keratinocyte; Papovaviridae; Gene expression; Onc gene
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204957

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.