R Thomas1, W A Anderson, V Raman, A H Reddi. 1. Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract
BACKGROUND: What is the molecular basis of the osteotrophic action of prostatic metastases? Demineralized bone matrix has the potential to induce new bone formation. The identification of bone morphogenetic proteins (BMPs) as the primary inducers of new bone formation in demineralized bone matrix has set the stage for studying prostate cancer-bone interrelationships. We have hypothesized that BMPs may be expressed in prostate and may be involved in the osteotrophic actions of metastatic prostate cancer cells. METHODS: Using polymerase chain reaction (PCR)-based quantitation, this study examined the presence of BMPs in mouse prostate and their potential regulation by orchidectomy and androgen replacement. RESULTS: BMP-7 and BMP-4 genes were expressed in mouse prostate. Quantitative PCR analysis showed that the BMP-7 mRNA level was significantly decreased following orchidectomy and increased by testosterone and dihydrotestosterone. Therefore, the BMP-7 mRNA level is androgen-dependent. On the other hand, BMP-4 was expressed constitutively in the prostate. CONCLUSIONS: The regulated expression of BMP-7 mRNA in the prostate suggests that BMP-7 may explain in part the stimulation of bone formation and osteosclerosis by metastatic prostate adenocarcinoma.
BACKGROUND: What is the molecular basis of the osteotrophic action of prostatic metastases? Demineralized bone matrix has the potential to induce new bone formation. The identification of bone morphogenetic proteins (BMPs) as the primary inducers of new bone formation in demineralized bone matrix has set the stage for studying prostate cancer-bone interrelationships. We have hypothesized that BMPs may be expressed in prostate and may be involved in the osteotrophic actions of metastatic prostate cancer cells. METHODS: Using polymerase chain reaction (PCR)-based quantitation, this study examined the presence of BMPs in mouse prostate and their potential regulation by orchidectomy and androgen replacement. RESULTS:BMP-7 and BMP-4 genes were expressed in mouse prostate. Quantitative PCR analysis showed that the BMP-7 mRNA level was significantly decreased following orchidectomy and increased by testosterone and dihydrotestosterone. Therefore, the BMP-7 mRNA level is androgen-dependent. On the other hand, BMP-4 was expressed constitutively in the prostate. CONCLUSIONS: The regulated expression of BMP-7 mRNA in the prostate suggests that BMP-7 may explain in part the stimulation of bone formation and osteosclerosis by metastatic prostate adenocarcinoma.
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