Bone morphognetic proteins (BMPs) and BMP receptor expression in breast cancer cells and their significance in bone metastases

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Breast cancer often cause osteoblastic bone metastasis, but its mechanisms are not elucidated. We investigated gene expression of BMPs and BMP receptors in breast cancer cells and the effect of BMP on those cells. RT-PCR analysis revealed that all human breast cancer tissue samples expressed several of examined BMP (2-7) mRNAs.. Immunoblot of conditioned media of those cell lines detected secretion of BMP-2. Correlation of BMP-6 mRNA expression in breast cancer samples and presense of bone metastases was found. All breast cancer samples examined expressed BMP-receptor type 1 and type 2 mRNAs. BMP-2 and BMP-4 inhibited growth of estrogen receptor (ER)-positive cells lines (MCF-7, ZR-75-1, T47D) at 10-200 ng/ml, and estradiol antagonized the inhibitory effect of BMP. BMP had no effect on ER activity in MCF-7 or T47D cells, but BMP inhibited phosphorylation of signal transducers and activators of transcription (stat)-3. These observations suggest that BMPs might have regulatory role in breast cancer cell growth and participate in interaction of can cer cell and bone microenvironment in bone metastasis.