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Transforming growth factor βs (TGFβs) were originally discovered due to their ability to promote anchorage-independent growth of rat NRK fibroblasts in the presence of TGFβ. TGFβ1, TGFβ2 and TGFβ3 are each synthesized as precursor proteins that are very similar in that each is cleaved to yield a 112 amino acid polypeptide that remains associated with the latent portion of the molecules. TGFβ3 mediates many intercellular interactions that occur during embryonic development, cell differentiation and epithelial homeostasis. TGFβ3 overexpresses in extramammary Paget s disease (EPD) and downregulates in Bowen s disease, indicating that its expression is a useful indicator of tumor activity. TGFβ3 levels strongly correlate with IGF-1 and osteocalcin levels in serum. Significant amounts of TGFβ3 circulation appear to be representative of TGFβ3 expression in bone and may in part be derived from bone. Glucocorticoids may block TGFβ production by modulating mRNA levels and c-Jun activity.
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