Role of Myc in differentiation and apoptosis in HL60 cells after exposure to arsenic trioxide or all-trans retinoic acid.
Acute promyelocytic leukemia (APL) is highly malignant and frequently expresses the PML-RARalpha (promyelocytic leukemia-retinoic acid receptor-alpha) fusion protein. This fusion protein is targeted by all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), presently used in APL therapy. We have evaluated effects of ATRA and As2O3 treatment in PML-RARalpha-negative HL60 promyelocytic leukemia cells, harboring amplified c-myc. Characterization of expression and activity of c-Myc and its target genes hTERT (human telomerase reverse transcriptase) and CAD (carbamoyltransferase-dihydroorotase) revealed marked down-regulation in response to ATRA, but not As2O3. We suggest that blockage of terminal differentiation upon As2O3 treatment may be mediated through c-Myc.
Jiang
Guosheng
G
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Albihn
Ami
A
Tang
Tianhua
T
Tian
Zhigang
Z
Henriksson
Marie
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D018922:HL-60 Cells; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001152:Arsenicals; C489427:MYC protein, human; D010087:Oxides; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014212:Tretinoin; D019098:Telomerase; D000077237:Arsenic Trioxide