Molecular mechanism of granulocytic differentiation of human promyelocytic leukemia HL-60 cells induced by all-trans retinoic acid.
OBJECTIVE
To elucidate the molecular mechanism of granulocytic differentiation of human promyelocytic leukemia HL-60 cells induced by all-trans-retinoic acid (ATRA).


METHODS
Flow cytometry was used to determine the cell cycle changes of HL-60 cells upon ATRA treatment. Gene expression profiles of HL-60 cells induced by 1 mumol.L-1 ATRA were obtained by using cDNA microarrays containing 9,984 genes and expressed sequence tags (ESTs).


RESULTS
Cell cycle analysis showed that 48%-73% of cells were arrested at G1/G0 phase upon ATRA treatment; cDNA microarray results demonstrated that the expression of genes encoding adhesion molecules, tissue remodeling proteins, transporters and ribosomal proteins were up-regulated in ATRA treated of HL-60 cells. Several genes involved in oxidase activation pathway were also differentially expressed.


CONCLUSIONS
ATRA treatment induced growth arrest and differentiation in HL-60 cells, which is associated with regulation of the oxidase activation pathway and the expression of tissue remodeling proteins.
Wang
Jin
J
Applied Research Center for Genomic Technology, Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong, China.
Tzeng
Chi-hung
CH
Huang
Ming-hui
MH
Fang
Hong-xun
HX
Xiao
Pei-gen
PG
Han
Rui
R
Yang
Meng-su
MS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology*; D018922:HL-60 Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D014212:Tretinoin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014212:Tretinoin