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Hepatocyte growth factor up-regulates the expression of the bone morphogenetic protein (BMP) receptors, BMPR-IB and BMPR-II, in human prostate cancer cells.
- Source :
-
International journal of oncology [Int J Oncol] 2007 Feb; Vol. 30 (2), pp. 521-9. - Publication Year :
- 2007
-
Abstract
- Hepatocyte growth factor (HGF) plays multiple roles in cancer, by acting as a motility, invasion and angiogenesis stimulating factor, which promotes metastasis and tumour growth. Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily. The effects of BMPs are mediated by two subgroups of receptors, type I and type II. Recent studies have shown that some BMPs, via their signaling pathways, affect the growth of prostate cancer cells. BMPR-IB and BMPR-II have been reported to be expressed at low levels in prostate cancer. However, little is known about the crosstalk between HGF and BMP pathways. In this study, prostate cancer cells (PC-3 and DU-145) were exposed to HGF at different concentrations (1-75 ng/ml) for 18 h, or were treated with HGF at 40 ng/ml over various time periods (up to 24 h). The effect of HGF on BMP receptor expression was further investigated in a nude mouse PC-3 xenograft model. Mice were treated with either HGF, the HGF antagonist NK4, or a combination of both. The expression of BMPR-IB and BMPR-II mRNA was up-regulated by HGF, as shown by both conventional PCR and quantitative PCR. An elevation of BMPR-IB and BMPR-II at the protein level was confirmed by both Western blot analysis and immunocytochemical staining. In a murine prostate tumour model, infusion of recombinant HGF resulted in an increase in the levels of both BMPR-IB and BMPR-II transcript in prostate tumours. Concomitant delivery of NK4, an HGF antagonist, prevented this effect. In conclusion, HGF up-regulates the expression of the bone morphogenetic protein receptors, BMPR-IB and BMPR-II, in prostate cancer cells, both in vitro and in vivo. This may have important implications in the development of bone metastasis in prostate cancer.
- Subjects :
- Animals
Cell Line, Tumor
Humans
Male
Mice
Neoplasm Metastasis
Neoplasm Transplantation
Signal Transduction
Bone Morphogenetic Protein Receptors, Type I biosynthesis
Bone Morphogenetic Protein Receptors, Type II biosynthesis
Bone Morphogenetic Proteins physiology
Bone Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Hepatocyte Growth Factor physiology
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1019-6439
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 17203235