HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Imaging transforming growth factor-beta signaling dynamics and therapeutic response in breast cancer bone metastasis.

Abstract
Although the transforming growth factor-beta (TGF-beta) pathway has been implicated in breast cancer metastasis, its in vivo dynamics and temporal-spatial involvement in organ-specific metastasis have not been investigated. Here we engineered a xenograft model system with a conditional control of the TGF-beta-SMAD signaling pathway and a dual-luciferase reporter system for tracing both metastatic burden and TGF-beta signaling activity in vivo. Strong TGF-beta signaling in osteolytic bone lesions is suppressed directly by genetic and pharmacological disruption of the TGF-beta-SMAD pathway and indirectly by inhibition of osteoclast function with bisphosphonates. Notably, disruption of TGF-beta signaling early in metastasis can substantially reduce metastasis burden but becomes less effective when bone lesions are well established. Our in vivo system for real-time manipulation and detection of TGF-beta signaling provides a proof of principle for using similar strategies to analyze the in vivo dynamics of other metastasis-associated signaling pathways and will expedite the development and characterization of therapeutic agents.
AuthorsManav Korpal, Jun Yan, Xin Lu, Shuwa Xu, Dorothy A Lerit, Yibin Kang
JournalNature medicine (Nat Med) Vol. 15 Issue 8 Pg. 960-6 (Aug 2009) ISSN: 1546-170X [Electronic] United States
PMID19597504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Smad4 Protein
  • Smad4 protein, mouse
  • Transforming Growth Factor beta
Topics
  • Animals
  • Bone Neoplasms (diagnosis, metabolism, secondary, therapy)
  • Breast Neoplasms (diagnosis, metabolism, pathology, therapy)
  • Diagnostic Imaging (methods)
  • Female
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • Models, Biological
  • Signal Transduction (drug effects)
  • Smad4 Protein (genetics, metabolism)
  • Transforming Growth Factor beta (pharmacokinetics)
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Validation Studies as Topic
  • Xenograft Model Antitumor Assays

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: