The Loss of TGF-β Signaling Promotes Prostate Cancer Metastasis
| Autor: | Naoya Masumori, Tania Z. Thomas, Harold L. Moses, William H. Tu, Yu Shyr, Susan Kasper, Scott B. Shappell, Richard L. Roberts, Neil A. Bhowmick, Agnieszka E. Gorska, Robert J. Matusik, Tom Case |
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| Rok vydání: | 2003 |
| Předmět: |
Genetically modified mouse
Cancer Research probasin Transgene transgenic mice Biology lcsh:RC254-282 Metastasis 03 medical and health sciences Prostate cancer 0302 clinical medicine Prostate medicine metastasis 030304 developmental biology 0303 health sciences Cancer transforming growth factor-β Transforming growth factor beta lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens prostate cancer medicine.disease 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Cancer research Transforming growth factor |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 5, Iss 3, Pp 267-277 (2003) |
| ISSN: | 1476-5586 |
| DOI: | 10.1016/s1476-5586(03)80058-1 |
| Popis: | In breast and colon cancers, transforming growth factor (TGF)-beta signaling initially has an antineoplastic effect, inhibiting tumor growth, but eventually exerts a proneoplastic effect, increasing motility and cancer spread. In prostate cancer, studies using human samples have correlated the loss of the TGF-beta type II receptor (T beta R II) with higher tumor grade. To determine the effect of an inhibited TGF-beta pathway on prostate cancer, we bred transgenic mice expressing the tumorigenic SV40 large T antigen in the prostate with transgenic mice expressing a dominant negative T beta R II mutant (DN II R) in the prostate. Transgene(s) and TGF-beta 1 expression were identified in the prostate and decreased protein levels of plasminogen activator inhibitor type I, as a marker for TGF-beta signaling, correlated with expression of the DN II R. Although the sizes of the neoplastic prostates were not enlarged, increased amounts of metastasis were observed in mice expressing both transgenes compared to age-matched control mice expressing only the large T antigen transgene. Our study demonstrates for the first time that a disruption of TGF-beta signaling in prostate cancer plays a causal role in promoting tumor metastasis. |
| Databáze: | OpenAIRE |
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