Abstract: |
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. |
Keywords: |
controlled study; human cell; antigen expression; cell cycle; cell cycle s phase; cell division; protein bcl 2; apoptosis; cell line; cell differentiation; transcription, genetic; tumor cells, cultured; protein p53; time factors; gene expression regulation; tumor suppressor gene; leukemia, promyelocytic, acute; gene expression regulation, neoplastic; kinetics; messenger rna; enzyme inhibitors; rna, messenger; cd11b antigen; acute myeloblastic leukemia; tumor suppressor protein p53; antigens, cd; cyclin-dependent kinase inhibitor p21; cyclins; cyclin dependent kinase inhibitor; proto-oncogene proteins c-bcl-2; retinoic acid; cell cycle g1 phase; burkitt lymphoma; p53; genes, p53; protein synthesis regulation; promyelocyte; bcl-2; mitosis inhibition; tretinoin; chromosome translocation 17; granulopoiesis; genes, bcl-2; humans; human; priority journal; article; macrophage-1 antigen; nb4 cells; chromosome translocation 15; waf1/p21
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