The Putative Oncoprotein Bcl-3 Induces Cyclin D1 To Stimulate G sub(1) Transition

• Published in: Molecular and cellular biology Vol. 21; no. 24; pp. 8428 - 8436
• Main Authors: Westerheide, S D, Mayo, M W, Anest, V, Hanson, J L, Baldwin Jr., AS
• Format: Journal Article
• Language: English
• Published: 01-12-2001
• Subjects: Bcl-3 protein; cyclin D1; G1 phase
• ISSN: 0270-7306
• DOI: 10.1128/MCB.21.24.8428-8436.2001

Bcl-3 is a distinctive member of the I Kappa B family of NF- Kappa B 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 sub(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- Kappa B p52 homodimers, was demonstrated to directly activate the cyclin D1 promoter through an NF- Kappa B binding site. Therefore, our results demonstrate that dysregulated expression of Bcl-3 potentiates the G sub(1) transition of the cell cycle by stimulating the transcription of the cyclin D1 gene in human breast epithelial cells.