RB Tumor Suppressor Gene Expression Responds to DNA Synthesis Inhibitors

Expression of the RB tumor suppressor gene, whose function is putatively in controlling cell growth, may be regulated by S-phase specific inhibitors of DNA synthesis that are commonly used in cell synchronization and cancer chemotherapy. Relatively low concentrations of the agents, cytosine arabinos...

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Bibliographic Details
Published in:In Vitro Cellular & Developmental Biology - Animal 1992-09, Vol.28A (9/10), p.669-672
Main Authors: Yen, Andrew, Susi Varvayanis
Format: Article
Language:English
Subjects:
Antimetabolites - pharmacology
Biological and medical sciences
Biotechnology
Bromodeoxyuridine - pharmacology
Cell cycle
Cell growth
Cells
Cellular differentiation
Cultured cells
Cytarabine - pharmacology
DNA
DNA - biosynthesis
Fluorouracil - pharmacology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Neoplastic - drug effects
Gene therapy
Genes, myc
Genes, Retinoblastoma
Health. Pharmaceutical industry
Hematopoietic stem cells
Humans
Hydroxyurea - pharmacology
Industrial applications and implications. Economical aspects
Leukemia, Promyelocytic, Acute
Low concentrations
Methotrexate - pharmacology
Rapid Communications in Cell Biology
Retinoblastoma genes
Tretinoin - pharmacology
Tumor Cells, Cultured
Tumor suppressor genes
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Summary:Expression of the RB tumor suppressor gene, whose function is putatively in controlling cell growth, may be regulated by S-phase specific inhibitors of DNA synthesis that are commonly used in cell synchronization and cancer chemotherapy. Relatively low concentrations of the agents, cytosine arabinoside, bromodeoxyuridine, 5-fluorouracil, hydroxyurea, methotrexate and retinoic acid, were tested. At low concentrations still permitting submaximal cell growth, these drugs all changed RB gene expression, causing either up or down regulation of RB expression to varying degrees. Despite their potential similarity as a class, the nucleotide analogues elicited differential effects. The drug-induced up or down regulation of RB expression did not correlate with changes in c-myc expression indicating that the changes are not a manifestation of general metabolic changes potentially associated with altered proliferation. Amongst the agents considered, retinoic acid was the only one that caused a significant parallel reduction in RB and c-myc expression in the HL-60 human promyelocytic leukemia cells tested. The results thus show that even low concentrations of DNA synthesis inhibitors can have unpredictable affects on expression of growth regulatory genes.
ISSN:0883-8364
2327-431X
1543-706X
DOI:10.1007/BF02631044