title: PTHrP inhibits BMP-6 expression through the PKA signaling pathway in breast cancer cells.
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.
  
  
  OBJECTIVE
  These experiments were designed to investigate the molecular mechanism of PTHrP regulating BMP-6 in breast cancer cells.
  
  
  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.
authors.affiliation: Laboratory of Molecular Genetics, Medical College, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Mi
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Ji-dong
authors.initials: JD
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.forename: Tian-hui
authors.initials: TH
authors.lastname: Zhu
mesh_terms: D015153:Blotting, Western; D055418:Bone Morphogenetic Protein 6 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation
chemical_list: D055418:Bone Morphogenetic Protein 6; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; C066079:parathyroid hormone-related protein (1-108); D017868:Cyclic AMP-Dependent Protein Kinases
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