Cloning of human bone morphogenetic protein type IB receptor (BMPR-IB) and its expression in prostate cancer in comparison with other BMPRs

Abstract

Bone metastasis is a common event in prostate cancer, and it is known that some of the bone morphogenetic proteins (BMPs) are expressed in prostate cancer cells, while no study on the expression of their receptors, BMPRs, has been reported. Here we report cloning and sequence analysis of the human BMPR-IB cDNA. We also analysed the expression of transcripts of three types of the BMPR genes in human tissues and prostate cancer cell lines. The BMPR-IB mRNA was present in various organs, but the highest level was found in the prostate. Moreover, the amount of BMPR-IB mRNA was signi®cantly low in prostate cancer tissues after androgen withdrawal and was also low in prostate cancer cell lines. RT ± PCR analysis showed that the BMPR-IB message was upregulated by androgen stimulation in the LNCaP cell line which expresses the androgen receptor. By contrast, the mRNA levels of BMPR-IA and BMPR-II were not signi®cantly dierent among non-cancerous and cancerous prostate tissues. It was also suggested that human BMPR-IA and BMPR-IB might have dierent biological functions in the prostate, although their sequences were 85.3% identical in the serine-threonine kinase domain.

Molecular cloning and functional analysis of cDNA encoding a rat leukemia inhibitory factor: towards generation of pluripotent rat embryonic stem cells

“…LIF gene expression occurs at di erent stages of development, usually at very low levels (data not shown). Comparing with a standard cDNA library screening method, our modi®ed cDNA selection method was shown to be more e ective for cloning a cDNA derived from a transcript whose expression level was too low to be detected by Northern blot analysis (Ide et al, 1997;Kishi et al, 1997;. Thus, our modi®ed cDNA selection method was used for isolation of a rat LIF cDNA clone containing complete coding sequence.…”

Bone Morphogenetic Protein-6 Promotes Osteoblastic Prostate Cancer Bone Metastases through a Dual Mechanism

“…These results were consistent with a later study by Hamdy et al (25), who reported that BMP-6 mRNA expression was detected exclusively in malignant epithelial cells in 20 of 21 patients (95%) with metastases, in 2 of 11 patients (18%) with localized cancer, and undetectable in 8 benign samples. In addition to BMP, there have been several reports on prostate cancer expression of BMPR; it seems that as prostate cancer progress, the cells down-regulate their own expression of BMPRs (50,51), which may be a protective mechanism as it has been shown that BMP-2 can inhibit prostate cancer cell proliferation (52). Taken together, these observations show that prostate cancer cells produce increasing levels of BMPs as they progress to a more aggressive phenotype.…”

The Transforming Growth Factor-β Type III Receptor Mediates Distinct Subcellular Trafficking and Downstream Signaling of Activin-like Kinase (ALK)3 and ALK6 Receptors

“…Among the BMP type I receptors, ALK3 and ALK6 are notable in that they share significant structural homology, with 85% identity in their kinase domain and 42% identity in their extracellular domain (Ide et al, 1997). In particular, the two receptors possess identical glycine-serine (GS)-rich domains and L45 loops, known structural elements essential for their kinase activation and Smad recognition, respectively.…”

“…The type II receptor in turn transphosphorylates the type I receptor activating its kinase activity. Subsequently, the type I receptors engage and phosphorylate their intracellular effectors, the BMP-responsive Smads (Smad1, -5, and -8), which upon phosphorylation, complex with Smad4 and accumulate in the nucleus to regulate the transcription of target genes.Among the BMP type I receptors, ALK3 and ALK6 are notable in that they share significant structural homology, with 85% identity in their kinase domain and 42% identity in their extracellular domain (Ide et al, 1997). In particular, the two receptors possess identical glycine-serine (GS)-rich domains and L45 loops, known structural elements essential for their kinase activation and Smad recognition, respectively.…”