Transcriptional and post-transcriptional regulation of c-myc, c-myb, and p53 during proliferation and differentiation of murine erythroleukemia cells treated with DFMO and DMSO

Journal Article · Sat Oct 01 04:00:00 EDT 1988 · Experimental Cell Research; (United States)

DOI:https://doi.org/10.1016/0014-4827(88)90390-4· OSTI ID:5464591

Klinken, S P; Holmes, K L; Morse, III, H C; Thorgeirsson, S S ^[1]

---

1. National Institutes of Health, Bethesda, MD (USA)

The proto-oncogenes myc, myb, and p53 produce nuclear proteins which have been implicated in the regulation of proliferation or differentiation in a number of systems. The expression of these proto-oncogenes was studied in murine erythroleukemia (MEL) cells during (i) normal replication, (ii) DMSO-induced differentiation and (iii) {alpha}-difluoromethylornithine (DFMO)-restricted cell division and differentiation. The RNA levels of c-myc, c-myb, and p53 were all elevated during normal cellular proliferation; only c-myc expression declined when the cells stopped dividing although the rate of transcription for the gene was unaltered. In contrast, treatment of the cells with DFMO resulted in gradual cessation of cell replication and a decrease in transcription of c-myc, c-myb and p53. When the MEL cells were induced to differentiate with dimethyl sulfoxide (DMSO), a transient reduction in c-myc and c-myb RNA levels occurred immediately prior to the G{sub 1} arrest with a concomitant decrease in transcriptional activity, while p53 mRNA production was elevated without an increase in transcription. The authors conclude that (i) c-myc, c-myb, and p53 are regulated independently at both the transcriptional and post-transcriptional levels, (ii) DFMO inhibits MEL cell proliferation and expression of several genes, including c-myc, c-myb, and p53 are regulated independently at both the transcriptional and post-transcriptional levels, (ii) DFMO inhibits MEL cell proliferation and expression of several genes, including c-myc, c-myb and p53, and (iii) DFMO suppresses terminal differentiation but is unable to alter proto-oncogene changes associated with the early stages of differentiation.

• OSTI ID: 5464591
• Journal Information: Experimental Cell Research; (United States), Journal Name: Experimental Cell Research; (United States) Vol. 178:2; ISSN ECREA; ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CELL CYCLE
CELL DIFFERENTIATION
CELL PROLIFERATION
DAYS LIVING RADIOISOTOPES
DISEASES
DMSO
GENE REGULATION
GENES
IMMUNE SYSTEM DISEASES
ISOTOPES
LEUKEMIA
LIGHT NUCLEI
MESSENGER-RNA
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ONCOGENES
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RNA
SULFOXIDES
TRANSCRIPTION
TUMOR CELLS