Expression and functional analysis of Bax inhibitor-1 in human breast cancer cells

Recently, deregulated expression of the anti‐apoptotic protein Bax inhibitor‐1 (BI‐1) has been shown in several human cancers. In this report, we show that BI‐1 is expressed at various levels in six different human breast cancer cell lines. In order to investigate the function of BI‐1 in oestrogen‐dependent MCF‐7, T‐47D and oestrogen‐independent MDA‐MB‐231 breast cancer cells, the RNA interference technique was used to knock down BI‐1 expression specifically. Suppression of BI‐1 expression caused a significant increase in spontaneous apoptosis in MDA‐MB‐231 cells, whereas MCF‐7 and T‐47D cells remained almost unaffected. Furthermore, BI‐1 expression analysis using a cancer profiling array showed up‐regulation of BI‐1 expression in cancer samples of breast, uterus and ovary, whereas down‐regulated BI‐1 expression was identified in stomach, colon, kidney, lung and rectal cancer. In addition, immunohistochemical studies using a BI‐1‐specific antibody on human breast cancer specimens also revealed that BI‐1 is expressed in the majority of cases. Moreover, to analyse whether BI‐1 expression is oestrogen receptor‐dependent, tumour cells were treated with oestradiol, ICI and tamoxifen: this showed no significant changes in BI‐1 expression. Taken together, our results demonstrate that BI‐1 expression is differentially deregulated in different cancers and that BI‐1 plays an important role in preventing certain breast cancer cells from undergoing apoptosis. Thus, the development of novel therapeutic strategies based on targeting BI‐1 gene expression in breast cancer could be restricted to selected individual cancer types. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.