@article{88436,
  keywords = {Animals, Base Sequence, Humans, signal transduction, Molecular Sequence Data, Promoter Regions, Genetic, Mice, Female, Breast Neoplasms, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta, Tumor Suppressor Proteins, Transcriptional Activation, Neoplasm Transplantation, Bone Neoplasms, Interleukin-11},
  author = {Yibin Kang and Wei He and Shaun Tulley and Gaorav Gupta and Inna Serganova and Chang-Rung Chen and Katia Manova-Todorova and Ronald Blasberg and William Gerald and Joan Massagu{\'e}},
  title = {Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway.},
  abstract = {<p>TGF-beta can signal by means of Smad transcription factors, which are quintessential tumor suppressors that inhibit cell proliferation, and by means of Smad-independent mechanisms, which have been implicated in tumor progression. Although Smad mutations disable this tumor-suppressive pathway in certain cancers, breast cancer cells frequently evade the cytostatic action of TGF-beta while retaining Smad function. Through immunohistochemical analysis of human breast cancer bone metastases and functional imaging of the Smad pathway in a mouse xenograft model, we provide evidence for active Smad signaling in human and mouse bone-metastatic lesions. Genetic depletion experiments further demonstrate that Smad4 contributes to the formation of osteolytic bone metastases and is essential for the induction of IL-11, a gene implicated in bone metastasis in this mouse model system. Activator protein-1 is a key participant in Smad-dependent transcriptional activation of IL-11 and its overexpression in bone-metastatic cells. Our findings provide functional evidence for a switch of the Smad pathway, from tumor-suppressor to prometastatic, in the development of breast cancer bone metastasis.</p>
},
  year = {2005},
  journal = {Proc Natl Acad Sci U S A},
  volume = {102},
  pages = {13909-14},
  month = {09/2005},
  issn = {0027-8424},
  doi = {10.1073/pnas.0506517102},
  language = {eng},
}