Clonal response of K562 leukemic cells to exogenous p21WAF1.
The p21WAF1 protein is involved in the control of cell differentiation and proliferation. We have previously shown that p21WAF1 is upregulated in normal, proliferating hematopoietic cells undergoing differentiation. Exogenous p21WAF1 has been reported to increase colony-formation by normal hematopoietic progenitors. We examined the effects of exogenous p21WAF1 on proliferation, differentiation, gene expression and colony-formation by K562 cells using an inducible p21WAF1 expression construct. Expression of the stathmin (oncoprotein 18) gene decreased within 24 h of p21WAF1 expression; Hox B4 expression increased. Four K562 subclones were derived which differed in their response to equivalent induction of p21WAF1. All four subclones exhibited growth arrest in response to p21WAF1 in liquid culture. Three of four clones developed cytoplasmic granulation and partial morphologic differentiation after p21WAF1 induction. One clone exhibited fewer morphologic features of differentiation following p21WAF1 induction and unlike other clones, colony formation in methlycellulose was not decreased by p21WAF1 expression in this clone. This indicates that additional cell-specific factors influence cellular fate in the presence of elevated p21WAF1.
Steinman
R A
RA
Department of Medicine, University of Pittsburgh School of Medicine, 211 Lothrop Street, E1052 Biomedical Science Tower, Pittsburgh, PA 15213, USA. steinman@pitt.edu
Yaroslavskiy
B
B
Kaplan
S S
SS
Goff
J P
JP
Shields
D S
DS
D002273:Carcinogens / Q000494:pharmacology; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D020014:K562 Cells; D008868:Microtubule Proteins; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D050777:Stathmin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
C493956:CDKN1A protein, human; D002273:Carcinogens; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008868:Microtubule Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C493995:STMN1 protein, human; D050777:Stathmin; D013755:Tetradecanoylphorbol Acetate