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Journal of Cancer Research and Clinical Oncology

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01.02.2011 | Original Paper

PTHrP inhibits BMP-6 expression through the PKA signaling pathway in breast cancer cells

verfasst von: Dong Mi, Ming Zhang, Ji-dong Yan, Jie Zhang, Xu Wang, Qing Wang, Shuang Yang, Tian-hui Zhu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2011

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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.

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Titel: PTHrP inhibits BMP-6 expression through the PKA signaling pathway in breast cancer cells
verfasst von: Dong Mi
Ming Zhang
Ji-dong Yan
Jie Zhang
Xu Wang
Qing Wang
Shuang Yang
Tian-hui Zhu
Publikationsdatum: 01.02.2011
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2011
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0883-y

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PTHrP inhibits BMP-6 expression through the PKA signaling pathway in breast cancer cells

Abstract

Background

Purpose

Methods and results

Conclusions

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Abstract

Background

Purpose

Methods and results

Conclusions

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