The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G(1) transition

Bcl-3 is a distinctive member of the IkappaB family of NF-kappaB inhibitors because it can function to coactivate transcription. A potential involvement of Bcl-3 in oncogenesis is highlighted by the fact that it was cloned due to its location at a breakpoint junction in some cases of human B-cell ch...

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Bibliographic Details
Published in:Molecular and cellular biology 2001-12, Vol.21 (24), p.8428-8436
Main Authors: Westerheide, S D, Mayo, M W, Anest, V, Hanson, J L, Baldwin, Jr, A S
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Binding Sites
Blotting, Northern
Blotting, Western
Breast - metabolism
Cell Cycle
Cell Division
Cell Line
Cell Nucleus - metabolism
Cell Separation
Cloning, Molecular
COS Cells
Cyclin D1 - metabolism
Epithelial Cells - metabolism
Flow Cytometry
G1 Phase
Gene Expression Regulation, Neoplastic
Humans
Leukemia, B-Cell - metabolism
Luciferases - metabolism
Mice
NF-kappa B - antagonists & inhibitors
Phosphorylation
Plasmids - metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins - metabolism
Retinoblastoma Protein - metabolism
Transcription Factors
Transfection
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Summary:Bcl-3 is a distinctive member of the IkappaB family of NF-kappaB inhibitors because it can function to coactivate transcription. A potential involvement of Bcl-3 in oncogenesis is highlighted by the fact that it was cloned due to its location at a breakpoint junction in some cases of human B-cell chronic lymphocytic leukemia and that it is highly expressed in human breast tumor tissue. To analyze the effects of Bcl-3 dysregulation in breast epithelial cells, we created stable immortalized human breast epithelial cell lines either expressing Bcl-3 or carrying the corresponding vector control plasmid. Analysis of the Bcl-3-expressing cells suggests that these cells have a shortened G(1) phase of the cell cycle as well as a significant increase in hyperphosphorylation of the retinoblastoma protein. Additionally, the cyclin D1 gene was found to be highly expressed in these cells. Upon further analysis, Bcl-3, acting as a coactivator with NF-kappaB p52 homodimers, was demonstrated to directly activate the cyclin D1 promoter through an NF-kappaB binding site. Therefore, our results demonstrate that dysregulated expression of Bcl-3 potentiates the G(1) transition of the cell cycle by stimulating the transcription of the cyclin D1 gene in human breast epithelial cells.
ISSN:0270-7306
DOI:10.1128/MCB.21.24.8428-8436.2001