Back to Search
Start Over
NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF
- Source :
- Nature medicine. 13(1)
- Publication Year :
- 2006
-
Abstract
- Advanced breast cancers frequently metastasize to bone, resulting in osteolytic lesions, yet the underlying mechanisms are poorly understood. Here we report that nuclear factor-kappaB (NF-kappaB) plays a crucial role in the osteolytic bone metastasis of breast cancer by stimulating osteoclastogenesis. Using an in vivo bone metastasis model, we found that constitutive NF-kappaB activity in breast cancer cells is crucial for the bone resorption characteristic of osteolytic bone metastasis. We identified the gene encoding granulocyte macrophage-colony stimulating factor (GM-CSF) as a key target of NF-kappaB and found that it mediates osteolytic bone metastasis of breast cancer by stimulating osteoclast development. Moreover, we observed that the expression of GM-CSF correlated with NF-kappaB activation in bone-metastatic tumor tissues from individuals with breast cancer. These results uncover a new and specific role of NF-kappaB in osteolytic bone metastasis through GM-CSF induction, suggesting that NF-kappaB is a potential target for the treatment of breast cancer and the prevention of skeletal metastasis.
- Subjects :
- Pathology
medicine.medical_specialty
Blotting, Western
Osteoclasts
Bone Neoplasms
Breast Neoplasms
Electrophoretic Mobility Shift Assay
Mice, SCID
Granulocyte
General Biochemistry, Genetics and Molecular Biology
Bone resorption
Cytokine Receptor Common beta Subunit
chemistry.chemical_compound
Mice
Breast cancer
Osteoclast
Osteogenesis
medicine
Animals
Humans
Regulation of gene expression
business.industry
NF-kappa B
Bone metastasis
Granulocyte-Macrophage Colony-Stimulating Factor
Mammary Neoplasms, Experimental
NF-κB
General Medicine
medicine.disease
Blotting, Northern
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
chemistry
Experimental pathology
Female
RNA Interference
business
Subjects
Details
- ISSN :
- 10788956
- Volume :
- 13
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature medicine
- Accession number :
- edsair.doi.dedup.....d972c9df92c22df3beb055fa5a119ffa