Modulation of p53, WAF1/p21 and BCL-2 expression during retinoic acid-induced differentiation of NB4 promyelocytic cells.
The NB4 cell line, established from a patient with APL, carries the t(15; 17) and undergoes differentiation along the granulocytic pathway when exposed to retinoic acid (RA). The NB4 cell line was used as a model for exploring the expression of genes and proteins implicated in growth regulation, differentiation and apoptosis during treatment with RA. NB4 cells undergo a series of cytological and molecular alterations during RA treatment--Day 1: cell differentiation marked by an increase in CD11b is evident. Day 2: WAF1/p21 mRNA and then protein rise, though they drop 2 days later. Day 3: the percentage of cells in S phase begins to decrease and G1 arrest begins. Day 4: p53 mRNA level and then protein levels fall. Day 5: CD11b/BCL-2 double staining cells are markedly reduced. No signs of apoptosis were observed after up to 8 days of treatment with RA. These results demonstrate that NB4 cells treated with RA rapidly differentiate and arrest at G1 phase concurrent with p53-independent WAF1/p21 induction; in addition, phenotypic differentiation appears to commence before changes in cell cycle progression. An explanation for the decrease in p53 as well as the lack of apoptosis immediately after BCL-2 downregulation will require further study.
Bocchia
M
M
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Xu
Q
Q
Wesley
U
U
Xu
Y
Y
Korontsvit
T
T
Loganzo
F
F
Albino
A P
AP
Scheinberg
D A
DA
D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D015703:Antigens, CD; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D016177:Macrophage-1 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014212:Tretinoin