TY - JOUR
T1 - PTHrP inhibits BMP-6 expression through the PKA signaling pathway in breast cancer cells
AU - Mi, Dong
AU - Zhang, Ming
AU - Yan, Ji Dong
AU - Zhang, Jie
AU - Wang, Xu
AU - Wang, Qing
AU - Yang, Shuang
AU - Zhu, Tian Hui
N1 - Funding Information:
Acknowledgments This work was supported by a grant from the National Nature Science Foundation of China to S. Yang (No. 30700471).
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - Antimitogenic effect
KW - BMP-6
KW - Breast cancer
KW - PTHrP
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U2 - 10.1007/s00432-010-0883-y
DO - 10.1007/s00432-010-0883-y
M3 - Article
C2 - 20401668
AN - SCOPUS:78751607564
SN - 0171-5216
VL - 137
SP - 295
EP - 303
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
IS - 2
ER -