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PMID: 6952199 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inducer-mediated commitment of murine erythroleukemia cells to differentiation: a multistep process.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 79 ·No. 2 ·1982-01-00 ·Pages 471-5

Chen Z, Banks J, Rifkind RA, Marks PA

Abstract

There are a number of agents which, when added to cultures of murine erythroleukemia cells (MELC), markedly increase the probability of commitment to express the characteristics of terminal erythroid differentiation, including loss of proliferative capacity and increased accumulation of globin mRNA and hemoglobin. Some characteristics of inducer-mediated commitment of MELC to terminal erythroid differentiation were examined by determining the effects of dexamethasone (an inhibitor of inducer-mediated MELC differentiation) and of hemin (an inducer of globin mRNA accumulation). Previously, it was shown that exposure of MELC to hexamethylene-bisacetamide (HMBA) leads to commitment, detectable within 12 hr. MELC cultured with both HMBA and dexamethasone do not express commitment. MELC transferred from culture with HMBA and dexamethasone to cloning medium without these agents express commitment to terminal erythroid differentiation, indicating that MELC retain a "memory" for some early HMBA-mediated changes leading to commitment which occur even in the presence of the inhibitory steroid. The kinetics of commitment in experiments in which exposure to HMBA is interrupted, or dexamethasone is added to the culture in HMBA, suggest that there is a rate-limiting step early in the commitment process. The memory for this step persists for more than one cell cycle. Addition of hemin to cultures with HMBA and dexamethasone initiated accumulation of globin mRNA but does not reverse the steroid-mediated inhibition of terminal cell division (that is, the cells retain their proliferative capacity). Inducer-mediated MELC commitment is associated with accumulation of the chromatin protein IP25; dexamethasone does not inhibit this accumulation. Accumulation of IP25 may be inducer-related, but it is not sufficient to cause expression of terminal erythroid differentiation.

MeSH Terms
Acetamides/antagonists & inhibitors,pharmacology Animals Cell Differentiation/drug effects Cell Division/drug effects Cell Line Chromatin/metabolism Dexamethasone/pharmacology Diamines/antagonists & inhibitors,pharmacology Erythropoiesis/drug effects Gene Expression Regulation/drug effects Globins/genetics Hemin/pharmacology Leukemia, Erythroblastic, Acute/pathology Mice RNA, Messenger/metabolism
Chemicals
Acetamides Chromatin Diamines RNA, Messenger Hemin Dexamethasone Globins hexamethylene bisacetamide
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chen Z
Banks J
Rifkind R A
Marks P A
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43 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.79.2.471
Published
1982-01-00
Pages
471-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC345765
Subset
IM
Grants
NCI NIH HHS · CA-08748 · United States
NCI NIH HHS · CA-13696 · United States
NCI NIH HHS · CA-18314 · United States
External Links
PubMed source DOI: 10.1073/pnas.79.2.471 PMC Full Text View journal details
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