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

Dong Mi, Ming Zhang, Ji Dong Yan, Jie Zhang, Xu Wang, Qing Wang, Shuang Yang, Tian Hui Zhu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)295-303
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume137
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

Keywords

  • Antimitogenic effect
  • BMP-6
  • Breast cancer
  • PTHrP

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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