Role of Myc in differentiation and apoptosis in HL60 cells after exposure to arsenic trioxide or all-trans retinoic acid.

Abstract

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.

• Authors: Guosheng Jiang, Ami Albihn, Tianhua Tang, Zhigang Tian, Marie Henriksson
• Journal: Leukemia research (Leuk Res) Vol. 32 Issue 2 Pg. 297-307 (Feb 2008) ISSN: 0145-2126 [Print] England
• PMID: 17706770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Arsenicals
• MYC protein, human
• Oxides
• Proto-Oncogene Proteins c-myc
• RNA, Messenger
• Tretinoin
• Telomerase
• Arsenic Trioxide

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Arsenic Trioxide
• Arsenicals (pharmacology)
• Blotting, Western
• Cell Differentiation (drug effects)
• Enzyme-Linked Immunosorbent Assay
• Gene Expression (drug effects)
• Gene Expression Profiling
• HL-60 Cells
• Humans
• Oxides (pharmacology)
• Proto-Oncogene Proteins c-myc (drug effects, metabolism)
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Telomerase (drug effects, metabolism)
• Tretinoin (pharmacology)