Transforming growth factor β signaling impairs neu-induced mammary tumorigenesis while promoting pulmonary metastasis Journal Article
| Authors: | Siegel, P. M.; Shu, W.; Cardiff, R. D.; Muller, W. J.; Massagué, J. |
| Article Title: | Transforming growth factor β signaling impairs neu-induced mammary tumorigenesis while promoting pulmonary metastasis |
| Abstract: | The influence of transforming growth factor β (TGF-β) signaling on Neu-induced mammary tumorigenesis and metastasis was examined with transgenic mouse models. We generated mice expressing an activated TGF-β type I receptor or dominant negative TGF-β type II receptor under control of the mouse mammary tumor virus promoter. When crossed with mice expressing activated forms of the Neu receptor tyrosine kinase that selectively couple to the Grb2 or Shc signaling pathways the activated type I receptor increased the latency of mammary tumor formation but also enhanced the frequency of extravascular lung metastasis. Conversely, expression of the dominant negative type II receptor decreased the latency of Neu-induced mammary tumor formation while significantly reducing the incidence of extravascular lung metastases. These observations argue that TGF-β can promote the formation of lung metastases while impairing Neu-induced tumor growth and suggest that extravasation of breast cancer cells from pulmonary vessels is a point of action of TGF-β in the metastatic process. |
| Keywords: | signal transduction; controlled study; protein expression; sequence deletion; nonhuman; protein function; proteins; animal cell; mouse; animals; mice; animal tissue; apoptosis; transforming growth factor beta; lung neoplasms; neoplasm proteins; nerve tissue proteins; gene function; tumor cells, cultured; time factors; animalia; mus musculus; mice, transgenic; cancer inhibition; tumor suppressor gene; lung metastasis; nucleotide sequence; transforming growth factor beta receptor; transforming growth factor beta1; receptors, transforming growth factor beta; adaptor proteins, signal transducing; pregnancy; tumor promotion; genes, erbb-2; breast carcinogenesis; mammary glands, animal; drosophila proteins; ubiquitin-protein ligases; mouse mammary tumor virus; grb2 adaptor protein; lactation; mammary neoplasms, experimental; adaptor proteins, vesicular transport; ligases; oncogene neu; mitotic index; transforming growth factor beta2; genes, dominant; activin receptors, type i; humans; female; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 100 |
| Issue: | 14 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2003-07-08 |
| Start Page: | 8430 |
| End Page: | 8435 |
| Language: | English |
| DOI: | 10.1073/pnas.0932636100 |
| PUBMED: | 12808151 |
| PROVIDER: | scopus |
| PMCID: | PMC166246 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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