Changes in gene expression associated with induced differentiation of erythroleukemia: Protooncogenes, globin genes, and cell division Journal Article


Authors: Ramsay, R. G.; Ikeda, K.; Rifkind, R. A.; Marks, P. A.
Article Title: Changes in gene expression associated with induced differentiation of erythroleukemia: Protooncogenes, globin genes, and cell division
Abstract: Hexamethylenebisacetamide (HMBA)-induced differentiation of murine erythroleukemia cells (MELC) is a multistep process involving an early latent period during which a number of metabolic changes have been detected, but the cells are not yet committed irreversibly to differentiate. Commitment is defined as the capacity of MELC to go on to express the program of terminal cell division and gene expression (such as the accumulation of globin mRNA) upon removal of the HMBA from the culture. In the presence of HMBA, a small proportion of MELC are committed by 10-12 hr and >90% by 48-60 hr. The present study shows that, during the initial 4 hr of culture, HMBA causes a marked decrease in c-myb and c-myc and an increase in c-fos mRNA levels. With continued culture, the decrease in c-myb and the increase in c-fos mRNA persists, while c-myc mRNA returns to control levels before the time that MELC begin to show irreversible differentiation. Dexamethasone, which blocks expression of HMBA-induced MELC differentiation, does not alter the early pattern of changes in protooncogene mRNA nor the sustained elevation of c-fos, but it does inhibit the continued suppression of c-myb allowing c-myb to return toward control levels. Hemin, which induces MELC to accumulate globins but does not initiate commitment to terminal cell division, does not alter these protooncogene mRNA levels. These studies suggest that, although the early decrease in c-myb and c-myc and increase in c-fos mRNAs may be involved in the multistep events leading to differentiation, the continued suppression of c-myb is critical for HMBA-induced MELC commitment to terminal cell division.
Keywords: nonhuman; animal cell; mouse; cell division; heredity; proto oncogene; gene expression; genetic transcription; cell differentiation; in vitro study; animalia; messenger rna; globin gene; murinae; radioisotope; oncogene c myc; oncogene c myb; differentiation; etiology; erythroleukemia; hexamethylenebisacetamide; priority journal; oncogene c fos; blood and hemopoietic system
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 83
Issue: 18
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1986-09-01
Start Page: 6849
End Page: 6853
Language: English
DOI: 10.1073/pnas.83.18.6849
PUBMED: 3462732
PROVIDER: scopus
PMCID: PMC386607
DOI/URL:
Notes: Article -- Export Date: 18 August 2021 -- Source: Scopus
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  1. Paul Marks
    186 Marks
  2. Richard Rifkind
    118 Rifkind