The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
TGF-β switches from tumor suppressor to prometastatic factor in a model of breast cancer progression
Open accessAbstract
The TGF-beta signaling network plays a complex role in carcinogenesis because it has the potential to act as either a tumor suppressor or a pro-oncogenic pathway. Currently, it is not known whether TGF-beta can switch from tumor suppressor to pro-oncogenic factor during the course of carcinogenic progression in a single cell lineage with a defined initiating oncogenic event or whether the specific nature of the response is determined by cell type and molecular etiology. To address this question, we have introduced a dominant negative type II TGF-beta receptor into a series of genetically related human breast-derived cell lines representing different stages in the progression process. We show that decreased TGF-beta responsiveness alone cannot initiate tumorigenesis but that it can cooperate with an initiating oncogenic lesion to make a premalignant breast cell tumorigenic and a low-grade tumorigenic cell line histologically and proliferatively more aggressive. In a high-grade tumorigenic cell line, however, reduced TGF-beta responsiveness has no effect on primary tumorigenesis but significantly decreases metastasis. Our results demonstrate a causal role for loss of TGF-beta responsiveness in promoting breast cancer progression up to the stage of advanced, histologically aggressive, but nonmetastatic disease and suggest that at that point TGF-beta switches from tumor suppressor to prometastatic factor.
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TGF-β and the TGF-β family: context-dependent roles in cell and tissue physiology
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Metadata
- Authors
- Tang, B., Vu, M., Booker, T., Santner, S. J., Miller, F. R., Anver, M. R., & Wakefield, L. M.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-10-01
- Volume
- 112
- Issue
- 7
- Pages
- 1116-1124
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2058297837
- Cited by
- 393
- References
- 34
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tang, B., Vu, M., Booker, T., Santner, S. J., Miller, F. R., Anver, M. R., & Wakefield, L. M. (2003). TGF-β switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. Journal of Clinical Investigation. https://doi.org/10.1172/jci200318899
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