Implication of CDK inhibitors p21 and p27 in the differentiation of HL-60 cells.
All-trans retinoic acid (ATRA) differentiates HL-60 cells into granulocyte-like cells and cellular proliferation is repressed markedly along with the morphological and physiological changes specific for cellular differentiation. To elucidate the implication of cyclin-dependent kinase (CDK) inhibitors during differentiation, we examined the expression of CDK inhibitors during the differentiation of HL-60 cells. The expression of p21 and p27 among the CDK inhibitors we examined increased during the differentiation induced with ATRA. Then, we established stable transformants of HL-60 cells expressing antisense RNA for p21 and p27 and examined the ability of these cells to differentiate into granulocyte-like cells. The extents of fully differentiated HL-60 cells transfected with genes for antisense RNA of p21 and p27 were only 53% and 60%, respectively, whereas 90% of the parental HL-60 cells differentiated by the ATRA treatment. These results suggest that increased expression of CDK inhibitors, p21 and p27, is necessary for the differentiation of HL-60 cells induced with ATRA.
Horie
Nobuyuki
N
Laboratory of Genetic Engineering, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Japan.
Mori
Tsuyoshi
T
Asada
Hidetsugu
H
Ishikawa
Aki
A
Johnston
Patrick G
PG
Takeishi
Keiichi
K
D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018922:HL-60 Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D054462:p21-Activated Kinases
D018797:Cell Cycle Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D014212:Tretinoin; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases