Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells.
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.
Ishii
Yuki
Y
Saitama Cancer Center Research Institute, 818 Komuro, Ina, Saitama 362-0806, Japan.
Kasukabe
Takashi
T
Honma
Yoshio
Y
D000225:Adenine / Q000031:analogs & derivatives / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D003583:Cytokinins / Q000494:pharmacology*; D018076:DNA, Complementary; D004224:Diterpenes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D007541:Isopentenyladenosine; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D014212:Tretinoin / Q000378:metabolism; D020298:U937 Cells; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; D003583:Cytokinins; D018076:DNA, Complementary; D004224:Diterpenes; D009363:Neoplasm Proteins; C103003:S100P protein, human; C423222:cotylenin A; C001478:N(6)-(delta(2)-isopentenyl)adenine; D014212:Tretinoin; D007541:Isopentenyladenosine; D002117:Calcitriol; D000225:Adenine