Journal article
Absence of phorbol ester-induced down-regulation of myc protein in the phorbol ester-tolerant mutant of HL-60 promyelocytes
Cancer research (Chicago, Ill.), Vol.49(19), pp.5329-5333
1989
PMID: 2670202
Abstract
The human promyelocytic 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-O-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.
Details
- Title: Subtitle
- Absence of phorbol ester-induced down-regulation of myc protein in the phorbol ester-tolerant mutant of HL-60 promyelocytes
- Creators
- David Gailani - Univ. Iowa hosp. clin., dep. internal medicine, Iowa City IA 52242, United StatesFrank J Cadwell - Univ. Iowa hosp. clin., dep. internal medicine, Iowa City IA 52242, United StatesPeter S O'Donnell - University of IowaRobert A Hromas - Univ. Iowa hosp. clin., dep. internal medicine, Iowa City IA 52242, United StatesDonald E Macfarlane - Univ. Iowa hosp. clin., dep. internal medicine, Iowa City IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.49(19), pp.5329-5333
- PMID
- 2670202
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- American Association for Cancer Research
- Language
- English
- Date published
- 1989
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094748802771
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