Functional analysis of thymosin beta-4 using over-expressing transgenic mice

Proc Amer Assoc Cancer Res, Volume 46, 2005 1057 Thymosin beta-4, an actin-binding 43 amino acid peptide, has multi-functional roles in cell physiology. It was first identified as a thymic maturation factor and recently has been shown to accelerate wound healing, hair growth, and angiogenesis. Furthermore, we found that thymosin beta-4 stimulates tumor growth and metastasis by induction of cell migration and vascular endothelial growth factor (VEGF)- mediated angiogenesis. Using a construct on the keratin 5 promoter, we have now developed thymosin beta-4 over-expressing transgenic mice to further study its functional roles. We are examining if the mouse will develop more spontaneous cancers or be more susceptible to tumor-promoting agents. The over-expression of thymosin beta-4 in the skin of transgenic mice was confirmed by both western blot and immunohistochemical analyses. The phenotype of thymosin beta-4 over-expressing mice was examined. Spontaneous tumors or developmental differences were not observed in any of the organs except the mice had unusually shaped teeth. The teeth have dull incisors and white color similar to the enamel complex deficient mice. Both wound healing and hair growth were accelerated in the thymosin beta-4 over-expressing mice. The susceptibility of these mice to cancer promoting agents was also evaluated, but thymosin beta-4 expression had no effect on tumor progression/formation. We conclude that thymosin beta-4 does affect certain developmental processes and can promote tumor metastasis, but that it is not oncogenic.