Development of TGF-β resistance during malignant progression
Transforming growth factor-β (TGF-β) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities activities such as proliferation and differentiation as well as a number of basic physiological functions. The effects of TGF-β are critically dependent on the expression and distribution of a family of TGF-β receptors, the TGF-β types I, II, and III. It is now know that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. The coding sequence of the type II receptor (RII) appears to render it uniquely, susceptible to DNA, replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-β RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-β RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-β RII gene may be a very critical step in the pathway of carcinogenesis.
Key wordsTGF-β TGF-β receptors TGF-β resistance Mutation Carcinogenesis
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