title: 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.
authors.affiliation: Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: C P
authors.initials: CP
authors.lastname: Hsu
authors.forename: C C
authors.initials: CC
authors.lastname: Yang
authors.forename: S D
authors.initials: SD
authors.lastname: Yang
mesh_terms: D016375:Antisense Elements (Genetics) / Q000235:genetics / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D004357:Drug Synergism; D004920:Erythropoiesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D038461:Proline-Directed Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016375:Antisense Elements (Genetics); D002087:Butyrates; D006427:Hemin; D038461:Proline-Directed Protein Kinases; D017346:Protein Serine-Threonine Kinases