Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RAR alpha fusion gene.
The interaction of an exogenous PML/RAR alpha fusion gene associated with acute promyelocytic leukaemia, with all-trans retinoic acid (ATRA) was examined in two lymphoid cell lines. L1210 and MOLT-4 cells were transfected with PML/RAR alpha cDNA in the expression vector pGD and stable transformants (L1210PML/RAR alpha and MOLT-4PML/RAR alpha) were selected with G418. ATRA inhibited the growth of these stable transformants, as assessed by [3H]thymidine incorporation, in a dose-dependent manner, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also induced apoptosis, as assessed by fragmentation of genomic DNA, in L121OPML/RAR alpha and MOLT-4PML/RAR alpha cells but not in control cells. The exogenous PML/RAR alpha fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines.
Maeda
Y
Y
Third Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Horiuchi
F
F
Miyatake
J
J
Sono
H
H
Tatsumi
Y
Y
Urase
F
F
Irimajiri
K
K
Horiuchi
A
A
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008214:Lymphocytes / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000494:pharmacology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin