A mechanism of apoptosis induced by all-trans retinoic acid on adult T-cell leukemia cells: a possible involvement of the Tax/NF-kappaB signaling pathway.
In this study, five single clones were randomly established by limiting dilution method from each of the HTLV-I positive T cell lines - HUT 102 and ATL-2, and examined for the all-trans retinoic acid (ATRA) sensitivity, respectively. For each clone, we found a significant correlation between the reduction in 3[H]-thymidine incorporation and the reduction in CD25 expression (r=0.701, P<0.05) following treatment with 10(-5) M ATRA for 48 h. Agarose gel electrophoresis revealed DNA fragmentation of the cell lines treated with ATRA, indicative of apoptosis. These results suggested that the tax gene in the HTLV-I genome might be a key molecule involved in cell proliferation and CD25 expression. Thereafter, we transfected the tax gene in the expression vector (pCMV-Tax-neo) into the HTLV-I(-) T cell line Jurkat and examined the effects of ATRA on cell growth. The results showed that ATRA sensitivity was acquired by the Jurkat cells transfected with the tax gene expression vector, but not in those transfected with the control vector. We also observed NF-kappaB transcriptional activity on Jurkat cells transfected with the tax gene by CAT assay in the presence or absence of ATRA. NF-kappaB transcriptional activity was decreased significantly on Jurkat cells transfected with the tax gene after ATRA treatment. Taken together, these results indicate that ATRA may affect or block the Tax/NF-kappaB signaling pathway in ATL cells.
Nawata
H
H
Third Department of Internal Medicine, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan
Maeda
Y
Y
Sumimoto
Y
Y
Miyatake
J
J
Kanamaru
A
A
D000328:Adult; D000368:Aged; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D002999:Clone Cells / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D016356:Gene Products, tax / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008722:Methods; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects* / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D016356:Gene Products, tax; D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D014212:Tretinoin; D004247:DNA