Modeling Transforming Growth Factor-ß Signaling in Cancer
The discovery of TGF-ß has impacted our understanding of human cancer. We find many events that become deregulated are associated with TGF-ß signaling. TGF-ß has been shown to be a master regulator in every human cancer type. Accordingly, antagonists of TGF-ß signaling are emerging as therapies for cancer. Mouse models revealed the now assumed role of TGF-ß as a tumor suppressor in normal tissue, as well as TGF-ß having tumor promoting or metastatic activity once tumors progress (Muraoka et al. J Clin Invest 109:1551–1559, 2002; Pierce et al. Proc Natl Acad Sci USA 92:4254–4258, 1995; Tang et al. Nat Med 4:802–807, 1998). Mouse models have not only contributed to our understanding of TGF-ß signaling, but have also identified that the diversity of TGF-ß action is only compounded further as we consider the cells of the tumor and the tumor microenvironment. This review examines the diverse role of TGF-ß in cancer as it has been revealed through transgenic mouse models. Due to the often apparently contrary roles of TGF-ß signaling in cancer initiation, progression, and metastasis, the results from the study of mouse models may suggest better ways to target therapeutics antagonizing TGF-ß signaling.
KeywordsMammary Gland Null Mouse Conditional Knockout Knockout Mouse Model Smad7 Expression
We apologize to those whose work we could not cite. Our work is supported by grants from the NIH GM079879 (to VRP) and CA108646 (to NAB).
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