Absence of Phorbol Ester-induced Down-Regulation of myc Protein in the Phorbol Ester-tolerant Mutant of HL-60 Promyelocytes

David Gailani, Frank J. Cadwell, Peter S. O'Donnell, Robert A. Hromas, Donald E. Macfarlane

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The human promyelocyte leukemia cell line HL-60 has an amplified number of copies of the protooncogene c-myc. It is induced to differentiate by exposure to the phorbol ester 12–0-tetradecanoyl phorbol-13-acetate (TPA). We have developed a mutant phorbol ester-tolerant (PET) line of HL-60 which undergoes a transient growth arrest but does not differentiate when exposed to TPA (Macfarlane et al~>Br. J. Haematol-, 68: 291–302, 1988). The defect is not due to a general failure of TPA-induced phosphorylation. In this paper, we show that exposing phorbol ester-sensitive (S) HL-60 cells to TPA caused the disappearance of the c-myc protein antigen (detected on Western blots) in 4 h, whereas TPA had no effect on the c-myc protein content of PET cells. Dimethyl sulfoxide caused the rapid disappearance of the myc antigen in both cells. PET cells had slightly more copies of the c-myc gene detected on Southern blots than S cells, c-myc mRNA was equally unstable in both cells, as determined by Northern blots following actinomycin D. TPA induced the down-regulation of c-myc mRNA in S cells to a greater extent than in PET cells. Dimethyl sulfoxide caused a rapid down-regulation of c-myc mRNA in both cell lines. This shows that PET cells have a defect in the mechanism by which protein kinase C regulates c-myc transcription. Our results provide further evidence that reduction in c-myc expression is necessary for differentiation to occur in HL-60 cells.

Original languageEnglish (US)
Pages (from-to)5329-5333
Number of pages5
JournalCancer Research
Volume49
Issue number19
StatePublished - Oct 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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