bcl-2 over-expression enhances NF-κB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells

bcl-2 expression is often associated with poor prognosis in several types of tumors; however, the role of this molecule in breast cancer is still controversial. We found earlier that over-expression of bcl-2 in a human breast-cancer cell line (MCF7(ADR)) enhances its tumorigenicity and metastatic potential by inducing metastasis-associated properties such as increased secretion of the matrix metalloproteinase-9 (mmp-9). In the present study, we investigated the effect of bcl-2 over-expression on the activity of the transcription factor NF-κB, an important regulator of genes involved in tumor progression and invasion. Transient transfection experiments indicate that over-expression of bcl-2 in the MCF7(ADR) cell line, enhances NF-κB-de pendent transcriptional activity. Mobility-shift analysis revealed an increase of NF-κB DNA-binding in bcl-2-over-expressing clones that correlated with lower levels of the NF-κB cytoplasmic inhibitor IκBα. Moreover, point mutations of 2 highly conserved ...