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.
Grzmil
Michal
M
Institute of Human Genetics, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany.
Kaulfuss
Silke
S
Thelen
Paul
P
Hemmerlein
Bernhard
B
Schweyer
Stefan
S
Obenauer
Silvia
S
Kang
Tae Won
TW
Burfeind
Peter
P
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling
D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D011506:Proteins; C484209:TMBIM6 protein, human