Article: article from journal or magazin.
Influence of HPV16 E2 and its localisation on the expression of matrix metalloproteinase-9.
International Journal of Oncology
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Infection with the high-risk HPV types 16 and 18 is the major cause of cervical cancer and plays a role in the development of certain head and neck and skin cancers. We have previously demonstrated that the Early Protein 2 of the Cottontail Rabbit papillomavirus (CRPV), required for skin carcinogenesis in a rabbit model, is able to induce the expression of a matrix metalloproteinase (MMP-9); a protease known to play a key role in invasion and metastasis. However, as of now we do not understand the underlying mechanism of activation nor relevance for the human system. Here, we report that high-risk human papillomavirus HPV16 E2 similar to our previously reported results on CRPV E2 activates the human MMP-9 promoter predominantly via the MEK1-ERK1/2-AP-1-signaling pathway. In addition this activation is associated with a nuclear sub-localisation of HPV16-E2 suggesting a nuclear protein-protein or protein-DNA interaction of E2 as the underlying mechanism of activation.
Amino Acid Sequence, Animals, Base Sequence, Cell Transformation, Neoplastic/genetics, Cell Transformation, Neoplastic/metabolism, Cells, Cultured, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Gene Expression Regulation, Enzymologic, Humans, MAP Kinase Kinase 1/metabolism, MAP Kinase Kinase 1/physiology, Matrix Metalloproteinase 9/genetics, Matrix Metalloproteinase 9/metabolism, Mice, Mitogen-Activated Protein Kinase 3/metabolism, Molecular Sequence Data, NIH 3T3 Cells, Oncogene Proteins, Viral/genetics, Oncogene Proteins, Viral/metabolism, Signal Transduction/physiology, Tissue Distribution, Transcription Factor AP-1/metabolism, Transcription Factor AP-1/physiology, Transfection
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