The putative oncoprotein Bcl-3 induces cyclin d1 to stimulate G(1) transition

Bcl-3 is a distinctive member of the I kappaB family of NF-KB inhibitors be cause it can function to coactivate transcription. A potential involvement of Bcl-3 in oncogenesis is highlighted by the fact that it was cloned due t o its location at a breakpoint junction in some cases of human B-cell chron ic lymphocytic leukemia and that it is highly expressed in human breast tum or tissue. To analyze the effects of Bcl-3 dysregulation in breast epitheli al cells, we created stable immortalized human breast epithelial cell lines either expressing Bcl-3 or carrying the corresponding vector control plasm id. 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 i n hyperphosphorylation of the retinoblastoma protein. Additionally, the cyc lin D1 gene was found to be highly expressed in these cells. Upon further a nalysis, Bcl-3, acting as a coactivator with NF-kappaB p52 homodimers, was demonstrated to directly activate the cyclin DI promoter through an NF-kapp aB binding site. Therefore, our results demonstrate that dysregulated expre ssion of Bcl-3 potentiates the G(1) transition of the cell cycle by stimula ting the transcription of the cyclin D1 gene in human breast epithelial cel ls.