Differential expression of ras protooncogenes during in vitro differentiation of human erythroleukemia cells.
We have compared the expression of the ras protooncogene family (H-, K-, and N-ras) in leukemia cell differentiation utilizing as a model K562 and HEL erythroleukemia cells treated either with 1-beta-arabinofuranosylcytosine or 12-O-tetradecanoylphorbol-13-acetate (TPA). 1-beta-D-Arabinofuranosylcytosine induced terminal erythroid differentiation of K562 cells, while TPA induced myeloid differentiation of K562 and HEL cells, resulting in myelomonocytic-like cells expressing macrophagic and megakaryocytic markers. H-ras mRNA levels showed a dramatic decrease in K562 cells subjected to erythroid and myelomonocytic differentiation. The same result was found at the protein level for p21H-ras. Expression of K-ras and N-ras in K562 cells also decreased with differentiation, although significant mRNA levels remained despite cessation of cell proliferation. The decrease in K-ras expression was greater for TPA-treated cells than for 1-beta-arabinofuranosylcytosine-treated cells. TPA-induced myelomonocytic differentiation in HEL cells also resulted in a dramatic down-regulation of H-ras mRNA levels. Thus, by using a leukemia cell line able to differentiate along two different lineages, our results reveal a lineage-specific modulation of ras gene family expression.
Delgado
M D
MD
Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
Quincoces
A F
AF
Gómez-Casares
M T
MT
Martínez
C A
CA
Cuadrado
M A
MA
Richard
C
C
León
J
J
D002454:Cell Differentiation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics* / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012333:RNA, Messenger; D003561:Cytarabine; D013755:Tetradecanoylphorbol Acetate