The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Transforming Growth Factor-β Stimulates Parathyroid Hormone-related Protein and Osteolytic Metastases via Smad and Mitogen-activated Protein Kinase Signaling Pathways
Open accessAbstract
Transforming growth factor (TGF)-beta promotes breast cancer metastasis to bone. To determine whether the osteolytic factor parathyroid hormone-related protein (PTHrP) is the primary mediator of the tumor response to TGF-beta, mice were inoculated with MDA-MB-231 breast cancer cells expressing a constitutively active TGF-beta type I receptor. Treatment of the mice with a PTHrP-neutralizing antibody greatly decreased osteolytic bone metastases. There were fewer osteoclasts and significantly decreased tumor area in the antibody-treated mice. TGF-beta can signal through both Smad and mitogen-activated protein (MAP) kinase pathways. Stable transfection of wild-type Smad2, Smad3, or Smad4 increased TGF-beta-stimulated PTHrP secretion, whereas dominant-negative Smad2, Smad3, or Smad4 only partially reduced TGF-beta-stimulated PTHrP secretion. When the cells were treated with a variety of protein kinases inhibitors, only specific inhibitors of the p38 MAP kinase pathway significantly reduced both basal and TGF-beta-stimulated PTHrP production. The combination of Smad dominant-negative blockade and p38 MAP kinase inhibition resulted in complete inhibition of TGF-beta-stimulated PTHrP production. Furthermore, TGF-beta treatment of MDA-MB-231 cells resulted in a rapid phosphorylation of p38 MAP kinase. Thus, the p38 MAP kinase pathway appears to be a major component of Smad-independent signaling by TGF-beta and may provide a new molecular target for anti-osteolytic therapy.
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Cites
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Massagué, J. (2008) · Cell · doi:10.1016/j.cell.2008.07.001 · Cited by 3,907
Transforming Growth Factor-β Signaling in Immunity and Cancer
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Metadata
- Authors
- Käkönen, S.-M., Selander, K. S., Chirgwin, J. M., Yin, J. J., Burns, S., Rankin, W. A., Grubbs, B. G., Dallas, M., Cui, Y., & Guise, T. A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 277
- Issue
- 27
- Pages
- 24571-24578
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2030798978
- Cited by
- 276
- References
- 62
- FWCI
- 5.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Käkönen, S.-M., Selander, K. S., Chirgwin, J. M., Yin, J. J., Burns, S., Rankin, W. A., Grubbs, B. G., Dallas, M., Cui, Y., & Guise, T. A. (2002). Transforming Growth Factor-β Stimulates Parathyroid Hormone-related Protein and Osteolytic Metastases via Smad and Mitogen-activated Protein Kinase Signaling Pathways. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m202561200
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