Bis induces growth inhibition and differentiation of HL-60 cells via up-regulation of p27.
- Author:
Yun Jee SEO
1
;
Mi Hee JEON
;
Jung Hee LEE
;
Yong Joon LEE
;
Ho Joong YOUN
;
Jeong Heon KO
;
Jeong Hwa LEE
Author Information
1. Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. leejh@catholic.ac.kr
- Publication Type:Case Report ; Research Support, Non-U.S. Gov't
- Keywords:
BAG3 protein, human;
cell differentiation;
cyclin-dependent kinase inhibitor p27;
HL-60 cells
- MeSH:
Carrier Proteins/*metabolism;
*Cell Differentiation;
Cell Proliferation;
Cell Shape;
Cells, Cultured;
Cyclin-Dependent Kinase Inhibitor p27/*metabolism;
Flow Cytometry;
Gene Expression;
HL-60 Cells;
Humans;
Research Support, Non-U.S. Gov't;
*Up-Regulation
- From:Experimental & Molecular Medicine
2005;37(6):624-630
- CountryRepublic of Korea
- Language:English
-
Abstract:
Bis (Bag-3, CAIR), a Bcl-2-interacting protein, promotes the anti-apoptotic activity of Bcl-2 and increased levels of Bis have been observed in several disease models. The involvement of Bcl-2 and some Bcl-2-binding proteins in differentiation has recently been reported. However, the relevance of Bis to cellular differentiation remains unknown. The findings herein show that Bis expression is up-regulated during the differentiation of HL-60 cells. To investigate the effect of Bis expression on differentiation, we established Bis-overexpressing HL-60 cells (HL-60-bis). HL-60-bis cells have a low nuclear: cytoplasmic ratio and indented nucleus in Wright- Giemsa staining, and an increased expression of CD11b in immunofluorescence study, indicating the promotion of differentiation. The overexpression of Bis also resulted in a retarded cell growth rate, accompanied by the accumulation of HL-60 cells at the G0/G1 phase of the cell cycle, which was sustained during the differentiation process. Western blot analysis revealed that the expression of p27, a representative inducer of cell cycle arrest at the G1 phase, was increased 2.5-fold in HL-60-bis cells compared to HL-60-neo cells. These results suggest that the Bis induced growth inhibition of HL-60 cells promotes G0/G1 phase arrest via up-regulation of p27, which seems to be a prerequisite for differentiation. Further studies will be required to define the exact roles of Bis on cellular differentiation more precisely.
