The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G1 transition

S. D. Westerheide, M. W. Mayo, V. Anest, J. L. Hanson, Jr Baldwin

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Bcl-3 is a distinctive member of the IκB family of NF-κB 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 G1 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-κB p52 homodimers, was demonstrated to directly activate the cyclin D1 promoter through an NF-κB binding site. Therefore, our results demonstrate that dysregulated expression of Bcl-3 potentiates the G1 transition of the cell cycle by stimulating the transcription of the cyclin D1 gene in human breast epithelial cells.

Original languageEnglish (US)
Pages (from-to)8428-8436
Number of pages9
JournalMolecular and cellular biology
Volume21
Issue number24
DOIs
StatePublished - Dec 13 2001

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Oncogene Proteins
Cyclin D1
bcl-1 Genes
Breast
Epithelial Cells
Cell Cycle
Retinoblastoma Protein
G1 Phase
B-Cell Chronic Lymphocytic Leukemia
Carcinogenesis
Plasmids
Binding Sites
Breast Neoplasms
Cell Line

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The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G1 transition. / Westerheide, S. D.; Mayo, M. W.; Anest, V.; Hanson, J. L.; Baldwin, Jr.

In: Molecular and cellular biology, Vol. 21, No. 24, 13.12.2001, p. 8428-8436.

Research output: Contribution to journalArticle

Westerheide, S. D. ; Mayo, M. W. ; Anest, V. ; Hanson, J. L. ; Baldwin, Jr. / The putative oncoprotein Bcl-3 induces cyclin D1 to stimulate G1 transition. In: Molecular and cellular biology. 2001 ; Vol. 21, No. 24. pp. 8428-8436.
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