| Download | - View accepted manuscript: Transforming growth factor-β1 is the predominant isoform required for breast cancer cell outgrowth in bone (PDF, 985 KiB)
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| DOI | Resolve DOI: https://doi.org/10.1038/onc.2008.454 |
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| Author | Search for: Mourskaia, A. A.; Search for: Dong, Z.; Search for: Ng, S.; Search for: Banville, M.1; Search for: Zwaagstra, J. C.1; Search for: O'Connor-McCourt, M. D.1; Search for: Siegel, P. M. |
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| Affiliation | - National Research Council of Canada. NRC Biotechnology Research Institute
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| Format | Text, Article |
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| Subject | antagonists & inhibitors; bone neoplasms; breast neoplasms; cells; DNA-binding proteins; female; genetics; genome; immunoenzyme techniques; immunology; metabolism; mice; mice, knockout; mice, nude; osteolysis; pathology; pharmaceutical; phosphorylation; physiology; prevention & control; protein; protein-serine-threonine kinases; protein isoforms; receptors, transforming growth factor beta; reverse transcriptase polymerase chain reaction; RNA; RNA, messenger; secondary; smad2 protein; transforming growth factor beta; transforming growth factor beta1; transforming growth factor beta3; TGFβ isoforms; breast cancer; ligand trap; bone microenvironment |
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| Abstract | Transforming growth factor (TGF)-β signaling is a potent modulator of the invasive and metastatic behavior of breast cancer cells. Indeed, breast tumor responsiveness to TGF-β is important for the development of osteolytic bone metastases. However, the specific TGF-β isoforms that promote breast cancer outgrowth in bone is unknown. We demonstrate that expression of a TGF-β ligand trap, which neutralizes TGF-β1 and TGF-β3, in MDA-MB-231 breast cancer cells diminished their outgrowth in bone and reduced the severity of osteolytic lesion formation when compared with controls. We further show that a reduction or loss of TGF-β1 expression within the bone microenvironment of TGF-β1+/- and TGF-β1-/- mice significantly reduced the incidence of breast tumor outgrowth compared with wild-type animals. Interestingly, those tumors capable of growing within the tibiae of TGF-β1- deficient mice had upregulated expression of all three TGF-β isoforms. Finally, breast cancer cells expressing the TGF-β ligand trap showed a pronounced reduction in their ability to form osteolytic lesions when injected into the tibiae of TGF-b1þ +/- mice. Thus, our studies show that both host- and tumor-derived TGF-β expression plays a critical role during the establishment and outgrowth of breast cancer cells in bone. |
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| Publication date | 2008-12-15 |
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| In | |
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| Language | English |
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| NRC number | NRCC 49582 |
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| NPARC number | 12919050 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | a5949b03-a910-4b00-923b-5b8e78e13282 |
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| Record created | 2009-11-10 |
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| Record modified | 2020-04-15 |
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