Human T-cell leukemia virus type I tax activates transcription of the human monocyte chemoattractant protein-1 gene through two nuclear factor-κB sites

N. Mori, A. Ueda, S. Ikeda, Y. Yamasaki, Y. Yamada, M. Tomonaga, S. Morikawa, R. Geleziunas, Teizo Yoshimura, N. Yamamoto

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Abstract

Infection by human T-cell leukemia virus type (HTLV) I leads to adult T-cell leukemia and is also associated with the neurodegenerative disease HTLV-I-associated myelopathy/tropical spastic paraparesis. Leukocytes are attracted to sites of inflammation by chemokines. One such chemokine is monocyte chemoattractant protein (MCP)-1, a member of the C-C subfamily of chemokines. We investigated whether HTLV-I infection causes up-regulation of MCP-1, which may in turn cause recruitment of leukocytes to HTLV-I-infected areas. We now report that MCP-1 mRNA levels are elevated in HTLV-I-infected T-cell lines, when compared with uninfected ones. We further confirmed secretion of MCP-1 by HTLV-I-infected T-cell lines. MCP-1 mRNA was also expressed in leukemic cells from patients with adult T-cell leukemia. The 5' transcriptional regulatory region of the MCP-1 gene was activated by the HTLV-I-encoded transactivator Tax in the human T-cell line Jurkat, in which endogenous MCP-1 is induced by Tax. By using site-specific point mutations, we have identified two closely spaced nuclear factor (NF)-κB sites, A1 and A2, to be important for Tax-mediated transactivation of the MCP-1 gene. Through the use of an electrophoretic mobility shift assay, we demonstrated that Tax induced NF-κB binding to both MCP-1 κB sites. This is the first report to demonstrate that Tax can transactivate the MCP-1 gene through the induction of NF-κB. Our results thus reveal how Tax disrupts the normally regulated MCP-1 gene and leads to its constitutive expression in HTLV-I-infected cells. These findings may have important implications for our understanding of HTLV-I-associated diseases.

Original languageEnglish
Pages (from-to)4939-4945
Number of pages7
JournalCancer Research
Volume60
Issue number17
Publication statusPublished - Sep 1 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mori, N., Ueda, A., Ikeda, S., Yamasaki, Y., Yamada, Y., Tomonaga, M., Morikawa, S., Geleziunas, R., Yoshimura, T., & Yamamoto, N. (2000). Human T-cell leukemia virus type I tax activates transcription of the human monocyte chemoattractant protein-1 gene through two nuclear factor-κB sites. Cancer Research, 60(17), 4939-4945.