Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia invasiveness

Abstract

Human T-cell leukemia virus type I (HTLV-I

Matrix Metalloproteinase-9 gene induction by a truncated oncogenic NF-κB2 protein involves the recruitment of MLL1 and MLL2 H3K4 histone methyltransferase complexes

“…MMP9 is also critical for B-CLL invasion and progression and has been defined as a prognostic factor in patients with nonHodgkin's lymphoma (Sakata et al, 2004;RedondoMunoz et al, 2006). The transcriptional induction of MMP9 is regulated by NF-kB in HTLV-I-or in Epstein-Barr virus-infected cells (Yoshizaki et al, 1998;Mori et al, 2002) as well as on TNFa stimulation in skeletal muscle cells (Srivastava et al, 2007). Although the classical, TAK1-and IKKb-dependent NF-kB-activating pathway is required for the TNFamediated MMP9 gene expression (Srivastava et al, 2007), it is unclear whether the alternative NF-kBactivating pathway is also involved in induction of MMP9 in lymphoma cells.…”

Activation of NF-κB by HTLV-I and implications for cell transformation

“…Among these genes are those encoding cytokines and cytokine receptors, apoptosis inhibitors, cell cycle regulators, immune receptors that belong to the tumor necrosis factor receptor (TNFR) family, transcription factors, and intracellular signaling molecules. Additionally, HTLV-I induces the expression of genes involved in cell immortalization and tumor metastasis (Mori et al, 2002a;Sinha-Datta et al, 2004;Sasaki et al, 2005). Thus, it is apparent that the oncogenic action of HTLV-I involves deregulation of diverse cellular genes.…”

Potential of tumour cells for delivering oncolytic viruses

“…Transformation of TILs with HTLV elements (Tax), for instance, results in their immortalization and in the acquisition of a more invasive phenotype, with upregulation of metalloproteases and extravasation through the endothelium. 41 On the other hand, the endotheliotropism of certain parvoviruses raises the possibility of using activated endothelial cells to deliver these agents. 42 Whether other precursor cells might be conditioned so as to transfer OVs to specific tissues remains to be explored.…”