[Effects of As2O3 on the BCR/ABL protein tyrosine phosphorylation in K562 cells].
OBJECTIVE
To explore the mechanisms of As2O3 inducing apoptosis and growth inhibition in K562 cells and provide theoretical basis for clinical application.


METHODS
The effects of As2O3 on BCR/ABL protein tyrosine phosphorylation(PTP) and its signal transduction as well as the expression of apoptosis-related genes were studied by means of immunoprecipitation, Western blot, biochemical method and immunofluorescence.


RESULTS
Tyrosine phosphorylation of several cellular proteins especially BCR/ABL protein was decreased by 1 mumol/L As2O3, but not by 0.1 mumol/L As2O3. As2O3 had no effect on PTP activity, downregulated the expression of JAK2 protein, but did not affect the expressions of STAT1 and STAT2 proteins and the STAT1 protein tyrosine phosphorylation. As2O3 had no effect on the expression of the apoptosis-related genes like Bcl-2, Bcl-xL/S, Bax, ICH-1L, p53, PARP, either, but downregulated PML protein expression in K562 cells.


CONCLUSIONS
As2O3 might induce K562 cell apoptosis and inhibit its growth by reducing tyrosine phosphorylation of cellular proteins especially BCR/ABL protein and/or by downregulating JAK2 protein expression to interfere with the BCR/ABL protein signal transduction.
Xiao
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D
Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Second Medical University, Shanghai 200025.
Sun
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G
Su
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H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2; D020014:K562 Cells / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D011518:Proto-Oncogene Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D000077237:Arsenic Trioxide