التفاصيل البيبلوغرافية
| العنوان: |
Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. |
| المؤلفون: |
Yibin Kang, Wei He, Shaun Tulley, Gupta, Gaorav P., Serganova, Inna, Chang-Rung Chen, Manova-Todorova, Katia, Blasberg, Ronald, Gerald, William L., Massagué, Joan |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 9/27/2005, Vol. 102 Issue 39, p13909-13914, 6p |
| مصطلحات موضوعية: |
TRANSCRIPTION factors, TUMORS, BONE metastasis, BREAST cancer, CELL proliferation, GENETIC mutation |
| مستخلص: |
TGF-β 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-β while retain- ing 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 demon- strate that Smad4 contributes to the formation of osteolytic bone metastases and is essential for the induction of IL-li, a gene implicated in bone metastasis in this mouse model system. Acti- vator protein-I is a key participant in Smad-dependent transcrip- tional activation of IL-il 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
