[Mechanism of tissue factor expression on NB4 cells down-regulated by all-trans retinoic acid and arsenic trioxide].
OBJECTIVE
To investigate molecular mechanism of tissue factor (TF) expression on acute promyelocytic leukemia cell line NB4 cells down-regulated by all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)).


METHODS
Cyclohexamide (CHX) inhibition test for de novo protein synthesis and actinomycin D (Act D) inhibition test for RNA synthesis were used to check the effect of ATRA on the TF expression. TF antigen of U937 cells transfected with pMSCV-PML-RARalpha treated with or without ATRA and As(2)O(3) was detected.


RESULTS
CHX treatment completely suppressed the down-regulation effect of ATRA on the TF mRNA expression, Act D inhibition test showed that half-life of TF mRNA in treated NB4 cells was shortened to about 30 min from that of around 60 min in untreated NB4 cells. The TF antigen contents in U937 cells transfected with pMSCV-PML-RARalpha were significantly higher than that in transfected U937 cells with retrovirus vector. Both ATRA and As(2)O(3) could down-regulate the TF antigen level in U937 cells transfected with or without PML-RARalpha.


CONCLUSIONS
The modulation of the TF mRNA expression in NB4 cells by ATRA might be indirect. TF mRNA destabilization was involved in the TF regulation process mediated by ATRA. Elevated TF antigen level in U937 cells transfected with pMSCV-PML-RARalpha may be related to the fusion protein PML-RARalpha. The down-regulation effect of ATRA and As(2)O(3) on the TF expression of U937 cells might not involve the fusion protein.
Guo
W
W
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Wang
H
H
Zhao
W
W
Qu
B
B
Pan
L
L
Zhu
J
J
Chu
H
H
Wang
X
X
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D013925:Thromboplastin / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D003609:Dactinomycin; D014212:Tretinoin; D013925:Thromboplastin; D003513:Cycloheximide; D000077237:Arsenic Trioxide