Human T-cell leukemia virus type 1 tax transactivates the matrix metalloproteinase 7 gene via JunD/AP-1 signaling

Biochim Biophys Acta. 2011 May;1813(5):731-41. doi: 10.1016/j.bbamcr.2011.02.002. Epub 2011 Feb 18.


Adult T-cell leukemia (ATL) is a T-cell malignancy associated with human T-cell leukemia virus type 1 (HTLV-1) and characterized by visceral invasion. Degradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial process in invasion of tumors and metastasis. MMP-7 (or matrilysin), is a "minimal domain MMP" with proteolytic activity against components of the extracellular matrix. To determine the involvement of MMP-7 in visceral spread in ATL, this study investigated MMP-7 expression in ATL. MMP-7 expression was identified in HTLV-1-infected T-cell lines, peripheral blood ATL cells and ATL cells in lymph nodes, but not in uninfected T-cell lines or normal peripheral blood mononuclear cells. MMP-7 expression was induced following infection of a human T-cell line with HTLV-1, and specifically by the viral protein Tax. Functionally, MMP-7 promoted cell migration of HTLV-1-infected T cells. The MMP-7 promoter activity was increased by Tax and reduced by deletion of the activator protein-1 (AP-1) binding site. Electrophoretic mobility shift assay showed high levels of AP-1 binding proteins, including JunD, in HTLV-1-infected T-cell lines and ATL cells, and Tax elicited JunD binding to the MMP-7 AP-1 element. Tax-induced MMP-7 activation was inhibited by dominant negative JunD and augmented by JunD/JunD homodimers. Short interfering RNA against JunD inhibited MMP-7 mRNA expression in HTLV-1-infected T-cell lines. These results suggest that the induction of MMP-7 by Tax is regulated by JunD and that MMP-7 could facilitate visceral invasion in ATL. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Neutralizing / pharmacology
  • Cell Line
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation, Leukemic / drug effects
  • Gene Products, tax / metabolism*
  • Human T-lymphotropic virus 1 / drug effects
  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / enzymology
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Matrix Metalloproteinase 7 / genetics*
  • Matrix Metalloproteinase 7 / metabolism
  • Phytohemagglutinins / pharmacology
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Signal Transduction* / drug effects
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / pathology
  • T-Lymphocytes / virology
  • Transcription Factor AP-1 / metabolism*
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics*


  • Antibodies, Neutralizing
  • Gene Products, tax
  • JunD protein, human
  • Phytohemagglutinins
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MMP7 protein, human
  • Matrix Metalloproteinase 7