Immediate Up-Regulation of the Calcium-Binding Protein S100P and Its Involvement in the Cytokinin-Induced Differentiation of Human Myeloid Leukemia Cells

Biochim Biophys Acta. 2005 Sep 10;1745(2):156-65. doi: 10.1016/j.bbamcr.2005.01.005. Epub 2005 Feb 9.


Cytokinins are important purine derivatives that act as redifferentiation-inducing hormones to control many processes in plants. Cytokinins such as isopentenyladenine (IPA) and kinetin are very effective at inducing the granulocytic differentiation of human myeloid leukemia HL-60 cells. We examined the gene expression profiles associated with exposure to IPA using cDNA microarrays and compared the results with those obtained with other inducers of differentiation, such as all-trans retinoic acid (ATRA), 1 alpha,25-dihydroxyvitamin D3 (VD3) and cotylenin A (CN-A). Many genes were up-regulated, and only a small fraction were down-regulated, upon exposure to the inducers. IPA and CN-A, but not ATRA or VD3, immediately induced the expression of mRNA for the calcium-binding protein S100P. The up-regulation of S100P was confirmed at the protein expression level. We also examined the expression of other S100 proteins, including S100A8, S100A9 and S100A12, and found that IPA preferentially up-regulated S100P at the early stages of differentiation. IPA-induced differentiation of HL-60 cells was suppressed by treatment with antisense oligonucleotides against S100P, suggesting that S100P plays an important role in cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / metabolism
  • Calcitriol / metabolism
  • Calcium-Binding Proteins / biosynthesis*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cell Line, Tumor
  • Cytokinins / pharmacology*
  • DNA, Complementary
  • Diterpenes / metabolism
  • Gene Expression Regulation, Neoplastic / physiology
  • HL-60 Cells
  • Humans
  • Isopentenyladenosine
  • Leukemia, Myeloid / metabolism*
  • Leukemia, Myeloid / pathology*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Oligonucleotide Array Sequence Analysis
  • Tretinoin / metabolism
  • U937 Cells
  • Up-Regulation*


  • Calcium-Binding Proteins
  • Cytokinins
  • DNA, Complementary
  • Diterpenes
  • Neoplasm Proteins
  • S100P protein, human
  • cotylenin A
  • N(6)-(delta(2)-isopentenyl)adenine
  • Tretinoin
  • Isopentenyladenosine
  • Calcitriol
  • Adenine