Centrosome amplification in adult T-cell leukemia and human T-cell leukemia virus type 1 Tax-induced human T cells.
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.
Nitta
Takayuki
T
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Kanai
Masayuki
M
Sugihara
Eiji
E
Tanaka
Masakazu
M
Sun
Binlian
B
Nagasawa
Toshiro
T
Sonoda
Shunro
S
Saya
Hideyuki
H
Miwa
Masanao
M
D002472:Cell Transformation, Viral / Q000235:genetics*; D018385:Centrosome / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D016356:Gene Products, tax / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000821:virology*
D016356:Gene Products, tax