Influence of HPV16 E2 and its localisation on the expression of matrix metalloproteinase-9

Int J Oncol. 2010 Aug;37(2):337-45. doi: 10.3892/ijo_00000682.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology*
  • 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*
  • Oncogene Proteins, Viral / physiology*
  • Signal Transduction / physiology
  • Tissue Distribution
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor AP-1 / physiology
  • Transfection

Substances

  • DNA-Binding Proteins
  • E2 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Transcription Factor AP-1
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 1
  • Matrix Metalloproteinase 9