Constitutive activation of transcription factor AP-1 in primary adult T-cell leukemia cells.
Human T-cell leukemia virus type-I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL). This study examined the status of the oncogenic transcription factor AP-1 in leukemic cells freshly isolated from patients with ATL. Leukemic cells from peripheral blood of all patients with ATL exhibited constitutive AP-1 DNA binding activity, whereas mononuclear cells from normal individuals did not. In agreement with previous studies, HTLV-I transforming protein, Tax, was found to stimulate the DNA binding activity of AP-1 in a T-cell line. However, HTLV-I genes, including Tax, were not significantly expressed in leukemic cells freshly obtained from patients with ATL. Moreover, all T-cell lines derived from leukemic cells of patients with ATL also displayed constitutive AP-1 DNA binding activity, but expressed little Tax protein. Thus, leukemic cells of patients with ATL appear to have Tax-independent mechanisms that induce AP-1 activity, both in vivo and in vitro. In antibody supershift experiments, AP-1 in fresh leukemic cells and ATL-derived cell lines were found to contain JunD. Consistently, all primary ATL cells and ATL-derived cell lines expressed high levels of JunD messenger RNA. Our results suggest that AP-1 is activated in leukemic cells of patients with ATL through a Tax-independent mechanism and this may play a role in the deregulated phenotypes of ATL leukemic cells. (Blood. 2000;95:3915-3921)
Mori
N
N
Department of Preventive Medicine and AIDS Research, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan. n-mori@net.nagasaki-u.ac.jp
Fujii
M
M
Iwai
K
K
Ikeda
S
S
Yamasaki
Y
Y
Hata
T
T
Yamada
Y
Y
Tanaka
Y
Y
Tomonaga
M
M
Yamamoto
N
N
D000328:Adult; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000378:metabolism; D016758:Genes, jun; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D016356:Gene Products, tax; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1