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Suppression of proline‐directed protein kinase F A expression potentiates erythroid differentiation of human myeloid leukemia cells
Author(s) -
Hsu ChihPing,
Yang ChuanChing,
Yang ShiawDer
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20000901)89:5<1004::aid-cncr9>3.0.co;2-0
Subject(s) - myeloid leukemia , medicine , myeloid , leukemia , cancer research , myeloid cells , protein kinase a , cellular differentiation , kinase , microbiology and biotechnology , immunology , biology , gene , biochemistry
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 ≈80% and ≈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 ≈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. Cancer 2000;89:1004–11. © 2000 American Cancer Society.