Cell cycle-independent down-regulation of BCL-2 protein expression in differentiating HL-60 cells.
To understand the relationship between bcl-2 protein expression and the cell cycle during the processes of differentiation, we examined bcl-2 protein levels expressed during cell cycle phases in differentiating HL-60 human leukemia cells by using a two-color flow cytometric method. In exponentially proliferating HL-60 cells bcl-2 protein was constitutively expressed throughout the cell cycle phases, but a small population of G0/G1 cells expressed decreased levels of protein as compared with other cell cycle phases. HL-60 cells can be induced to differentiate to granulocytic pathway by retinoic acid or dimethylsulfoxide, and to monocytic/macrophagic pathway by 1, 25 dihydroxyvitamin D3 or 12-O-tetradecanoylphorbol -13-acetate. During treatment with any of these inducing agents, bcl-2 protein expression was time-dependently down-regulated after 24 h. A two-color flow cytometric analysis revealed that this down-regulation occurred throughout cell cycle phases, indicating that bcl-2 protein expression was down-regulated in cell cycle-independent manner during induction of differentiation in HL-60 cells. To our knowledge, this is the first demonstration suggesting that the regulation of bcl-2 protein expression is not related to the cell cycle during induction of differentiation in HL-60 cells.
Kumakura
S
S
Third Division of Internal Medicine, Shimane Medical University, Izumo, Japan. kumakura@shimane-med.ac.jp
Ishikura
H
H
Tsumura
H
H
Nakashima
A
A
Sato
Y
Y
Kobayashi
S
S
D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D015536:Down-Regulation; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000502:physiology
D019253:Proto-Oncogene Proteins c-bcl-2