Dichotomy of all-trans retinoic acid inducing signals for adult T-cell leukemia.
We previously reported that all-trans retinoic acid (ATRA) inhibits growth in human T-cell leukemia virus type 1 (HTLV-1)-positive T-cell lines and fresh cells from patients with adult T-cell leukemia. However, the mechanism of this inhibition is not clear. In the present study, we observed that NF-kappaB transcriptional activity as well as cell growth decreased significantly in HTLV-1-positive T-cell lines in the presence of ATRA. Furthermore, we observed that ATRA reduced HTLV-1 proviral DNA, HTLV-1 genes (gag, tax, or pol mRNA) using the real-time quantitative polymerase chain reaction. SIL-2R was reduced by ATRA in both protein level (culture supernantant) and mRNA level in HTLV-1-positive T-cell lines. Interestingly, ATRA significantly inhibited RT activity similar to azidothimidine (AZT) in HTLV-1-positive T-cell lines. Moreover, AZT inhibited proviral DNA but not NF-kappaB transcriptional activity, and sIL-2R on HTLV-1; however, ATRA inhibited of NF-kappaB, proviral DNA and sIL-2R on HTLV-1. These results suggested that the decrease in sIL-2R induced by ATRA may be caused by the actions of a NF-kappaB inhibitor acting on the NF-kappaB/sIL-2R signal pathway. These results suggested that ATRA could have two roles, as a NF-kappaB inhibitor and as an RT inhibitor.
Yamaguchi
T
T
Department of Hematology, Kinki University School of Medicine, Osaka 589-8511, Japan.
Maeda
Y
Y
Ueda
S
S
Hijikata
Y
Y
Morita
Y
Y
Miyatake
J-i
JI
Matsuda
M
M
Kanamaru
A
A
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006800:Deltaretrovirus Infections / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015683:Gene Products, gag / Q000235:genetics; D015684:Gene Products, pol / Q000235:genetics; D016355:Genes, pX / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000254:growth & development; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism; D011533:Proviruses / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012995:Solubility; D015533:Transcriptional Activation / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D019562:Viral Load
D000970:Antineoplastic Agents; D015683:Gene Products, gag; D015684:Gene Products, pol; D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D014212:Tretinoin