Bone morphogenetic protin (BMP) and their receptors in prostate cancer.

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Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-b (TGF-b) family and have been identified as factors which stimulate bone formation in vivo. They turned out to be multifunctional molecules regulating the growth, differentiation and apoptosis in various target cells. Some BMPs and their receptors (BMPRs) are expressed on prostate cancer cells. We have previously reported that BMPR-IB mRNA expression is highest in the prostate, a characteristic which is not shared by the other BMPRs, BMPR-IA and -II.However, the amounts of BMPR-IB mRNA were significantly low in prostate tissues after androgen withdrawal therapy. They were also low in prostate cancer cell lines. Semi-quantitative RT-PCR showed that BMPR-IB mRNA was induced by androgen in the androgen-sensitive human prostatic cancer cell line LNCaP, while the expression of BMPR-IA and -II mRNAs was not affected by androgen. When the recombinant human BMP-2 was added to the LNCaP cells in the presence of androgen, the cell growth was inhibited. In contrast, the growth rate was increased by addition of the same ligand, when the cells were cultured in the absence of androgen ; under this condition, the amounts of BMPR-IB mRNA were significantly decreased. These observations showed that the amounts of BMPR-IB, but not those of BMPR-IA were regulated by androgen and further suggest that BMPR-IA and BMPR-IB differentially modulate prostate cancer cell growth in response to BMP under different hormonal conditions ; BMPR-IA elicits growth stimulation and BMPR-IB conveys negative regulatory signal in response to BMP-2. We also examined the chromosome localization of BMPR-IA and -IB gene.By in situ hybridization and radiation hybrid mapping, we showed that the assignment of the BMPR-IA and BMPR-IB genes to human chromosome 10q22.3 and 4q23-q24.