Centrosome amplification in adult T-cell leukemia and human T-cell leukemia virus type 1 Tax-induced human T cells

Cancer Sci. 2006 Sep;97(9):836-41. doi: 10.1111/j.1349-7006.2006.00254.x. Epub 2006 Jun 29.

Abstract

Centrosomes play pivotal roles in cell polarity, regulation of the cell cycle and chromosomal segregation. Centrosome amplification was recently described as a possible cause of aneuploidy in certain solid tumors and leukemias. ATL is a T-cell malignancy caused by HTLV-1. Although the precise mechanism of cell transformation is unclear, the HTLV-1-encoded protein, Tax, is thought to play a crucial role in leukemogenesis. Here we demonstrate that lymphocytes isolated from patients with ATL show centrosome amplification and that a human T cell line shows centrosome amplification after induction of Tax, which was suppressed by CDK inhibitors. Micronuclei formation was also observed after centrosome amplification in Tax-induced human T cells. These findings suggest that Tax deregulates CDK activity and induces centrosome amplification, which might be associated with cellular transformation by HTLV-1 and chromosomal instability in HTLV-1-infected human T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Viral / genetics*
  • Centrosome / physiology*
  • Fluorescent Antibody Technique
  • Gene Products, tax / genetics*
  • Gene Products, tax / metabolism
  • Humans
  • Immunoblotting
  • Jurkat Cells
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • T-Lymphocytes / virology*

Substances

  • Gene Products, tax