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Suppression of proline-directed protein kinase F(A) expression potentiates erythroid differentiation of human myeloid leukemia cells.

Abstract：

BACKGROUND:Initial clinic studies revealed that the overexpression of proline-directed protein kinase F(A) (PDPK F(A)) is associated conversely with various stages of tumor tissue differentiation. However, the role of overexpressed PDPK F(A) in tumor cell differentiation remains unknown and needs to be established. In this report, the authors explore the potential role of PDPK F(A) in cellular differentiation by investigating the effects of partial inhibition of this kinase on erythroid differentiation of chronic myeloid leukemia cells (K562). METHODS:PDPK F(A) antisense expression vector and its specific antibody were developed successfully. Two stable, transfected antisense clones of human myeloid leukemia cells were subcloned that expressed approximately 80% and approximately 50% of the total PDPK F(A) existing in control-transfected clones, as determined by both immunoprecipitate activity assay and immunoblot analysis. In sharp contrast, the PDPK F(A) antisense clones expressed no significant suppression of any other related PDPK members' expression, demonstrating the specificity of these two antisense clones. RESULTS:The antisense clones proportionally induced spontaneous erythroid differentiation up to approximately 30% of the total K562 cells. Moreover, antisense suppression of PDPK F(A) expression appeared to potentiate sodium butyrate/hemin-induced erythroid differentiation of K562 cells to a more complete stage compared with the control. CONCLUSIONS:The results demonstrate that specific antisense suppression of overexpressed PDPK F(A) in human myeloid leukemia cells is sufficient to potentiate both spontaneous and drug-induced erythroid differentiation, indicating that PDPK F(A) is an important negative regulator in controlling the erythroid differentiation of human myeloid leukemia cells.

journal_name

Cancer

journal_title

Cancer

authors

Hsu CP,Yang CC,Yang SD

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

1004-11

issue

eissn

0008-543X

issn

1097-0142

pii

10.1002/1097-0142(20000901)89:5<1004::AID-CNCR9>3.

journal_volume

pub_type

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Suppression of proline-directed protein kinase F(A) expression potentiates erythroid differentiation of human myeloid leukemia cells.