Ectopic EBP2 expression enhances cyclin E1 expression and induces chromosome instability in HEK293 stable clones

Ming-Cheng Lee; Chang-Hsun Hsieh; Shu-Chen Wei; Shu-Chen Shen; Chiung-Nien Chen; Vin-Cent Wu; Li-Ying Chuang; Fon-Jou Hsieh; C H Herbert Wu; Jyy-Jih Tsai-Wu

doi:10.5483/bmbrep.2008.41.10.716

Ectopic EBP2 expression enhances cyclin E1 expression and induces chromosome instability in HEK293 stable clones

BMB Rep. 2008 Oct 31;41(10):716-21. doi: 10.5483/bmbrep.2008.41.10.716.

Authors

Ming-Cheng Lee¹, Chang-Hsun Hsieh, Shu-Chen Wei, Shu-Chen Shen, Chiung-Nien Chen, Vin-Cent Wu, Li-Ying Chuang, Fon-Jou Hsieh, C H Herbert Wu, Jyy-Jih Tsai-Wu

Affiliation

¹ Institute of Molecular Medicine, College of Medicine, National Taiwan University Hospital.

PMID: 18959818
DOI: 10.5483/bmbrep.2008.41.10.716

Abstract

To explore the effects of deregulated expression of the EBNA1 binding protein 2 (EBP2) on cell growth, we generated human HEK293 stable clones constitutively expressing an EBP2-EGFP fusion protein. We found both RNA and protein levels of cyclin E1, a dominant oncoprotein, were elevated in the EBP2- EGFP stable clones. These findings were confirmed by flow cytometry bivariate analysis of cyclin expression versus DNA content. Moreover, the increase in p21 expression and the specific phosphorylation at Ser1981 of ATM and Ser15 of p53 were also observed in these stable clones, and these observations may explain the failure to observe an increase in Cdk2 kinase activity. In addition, after one year of passage culture, the EBP2-EGFP stable clones tended to lose 4 to 5 chromosomes per cell when compared to that of control cells. All of these findings provide a possible link between deregulated expression of EBP2 and tumor development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ataxia Telangiectasia Mutated Proteins
Carrier Proteins / metabolism*
Cell Cycle Proteins / metabolism
Cell Line
Chromosomal Instability*
Chromosomes, Human / metabolism
Clone Cells
Cyclin E / metabolism*
Cyclin-Dependent Kinase 2 / metabolism
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
DNA-Binding Proteins / metabolism
Green Fluorescent Proteins / metabolism
Humans
Oncogene Proteins / metabolism*
Protein Serine-Threonine Kinases / metabolism
RNA-Binding Proteins
Recombinant Fusion Proteins / metabolism
Tumor Suppressor Protein p53 / metabolism
Tumor Suppressor Proteins / metabolism

Substances

CCNE1 protein, human
Carrier Proteins
Cell Cycle Proteins
Cyclin E
Cyclin-Dependent Kinase Inhibitor p21
DNA-Binding Proteins
EBNA1BP2 protein, human
Oncogene Proteins
RNA-Binding Proteins
Recombinant Fusion Proteins
Tumor Suppressor Protein p53
Tumor Suppressor Proteins
enhanced green fluorescent protein
Green Fluorescent Proteins
ATM protein, human
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases
CDK2 protein, human
Cyclin-Dependent Kinase 2