title: Growth arrest and apoptosis in adult T cell leukemia cell lines following IL-2 deprivation.
abstract: Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type-I (HTLV-I). Since ATL cells often require IL-2 for their proliferation and survival, we examined the effect of IL-2 deprivation on the IL-2-dependent ATL cells established from ATL patients. After IL-2 withdrawal, these cells were arrested in the G1 phase and then underwent apoptosis. p27Kip1 was observed to act as a cell cycle inhibitor. A decrease in the amount of Bcl-xL was more distinct than that of Bcl-2, while Bax increased slightly during IL-2 withdrawal. The activation of caspase-3 and the loss of mitochondrial membrane potential were also observed. An overexpression of Bcl-xL protein in the KK1, one of the ATL cell lines, suppressed apoptosis by the 3rd day, however, apoptosis could not be prevented completely. Thereafter, a decrease in Bcl-xL and an activation of caspase-3 were observed even under the overexpression of Bcl-xL. The mitochondrial membrane potential and the intra-cellular levels of reactive oxygen species (ROS) also changed due to IL-2 deprivation. From these results, the IL-2 signals are considered to be essential for the survival of ATL cells, and the interruption of IL-2 signaling might thus be useful as a potentially new treatment for ATL.
authors.affiliation: Molecular Oncology Center, Department of Laboratory Medicine, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan. fujimura@minf.med.fukuoka-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujimura
authors.forename: Fumiko
authors.initials: F
authors.lastname: Arakawa
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Liao
authors.forename: Pranay D
authors.initials: PD
authors.lastname: Khare
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
authors.forename: Junko
authors.initials: J
authors.lastname: Ono
mesh_terms: D000328:Adult; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004789:Enzyme Activation; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000473:pathology; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D051020:bcl-X Protein
chemical_list: C494811:BCL2L1 protein, human; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases