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PTHrP inhibits BMP-6 expression through the PKA signaling pathway in breast cancer cells.
- Source :
-
Journal of Cancer Research & Clinical Oncology . Feb2011, Vol. 137 Issue 2, p295-303. 9p. - Publication Year :
- 2011
-
Abstract
- Background: PTHrP, a mediator of humoral hypercalcemia of malignancy, is considered as a potential activator to induce breast cancer cells metastasizing to bone. However, recent clinical evidences and basal research results prove that PTHrP expression in primary tumors indicates good prognosis. BMP-6, as a member of TGF-β superfamily, is closely correlated with tumor differentiation and skeletal metastasis. Purpose: These experiments were designed to investigate the molecular mechanism of PTHrP regulating BMP-6 in breast cancer cells. Methods and results: Through detecting mRNA expression levels of PTHrP and BMP-6 in 35 breast cancer specimens, the two genes' expression were proved to be negatively correlated. Moreover, PTHrP (1-40), instead of PTHrP (107-139), inhibited BMP-6 mRNA expression in MCF-7 cells, indicating that PTHrP exerts its effect on BMP-6 through membranous PTHrP receptor. Inhibitors against signaling pathways downstream of PTHrP were utilized. H89, the PKA pathway inhibitor, eliminated the inhibitory effect of PTHrP on BMP-6. In addition, silencing of BMP-6 strengthened the antimitogenic effect of PTHrP. Conclusions: These results suggest that PTHrP acts as the upstream molecule of BMP-6, and exerts antimitogenic effect via reducing BMP-6 mRNA expression through PKA signaling pathway in breast cancer cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01715216
- Volume :
- 137
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Journal of Cancer Research & Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 57242646
- Full Text :
- https://doi.org/10.1007/s00432-010-0883-y