sirolimus and thymosin-beta(4)

Thymosin beta4, a major G-actin-sequestering protein, is known to be involved in tumor metastasis. In the present study, we found that thymosin beta4 expression promotes the formation of actin-based pseudopodia-like extensions, associated with cell migration, in human prostate cancer LNCaP cells. Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin and Cdc42/Rac1/RhoA inhibitor Clostridium difficile toxin B significantly reduced pseudopodia formation in thymosin beta4-overexpressing LNCaP cells, suggesting that the pseudopodia formation by thymosin beta4 is probably involved in PI3K and Rho family pathway. We recently reported that thymosin beta4 expression is upregulated by androgen deprivation in prostate cancer cells. The increase in thymosin beta4 may be one of the causes of prostate cancer progression after androgen ablation therapy.

Topics: Androstadienes; Bacterial Proteins; Bacterial Toxins; Butadienes; cdc42 GTP-Binding Protein; Cell Line, Tumor; Cell Movement; Humans; Male; Microscopy, Phase-Contrast; Nitriles; Phosphoinositide-3 Kinase Inhibitors; Prostatic Neoplasms; Pseudopodia; rac1 GTP-Binding Protein; Reverse Transcriptase Polymerase Chain Reaction; rhoA GTP-Binding Protein; Sirolimus; Thymosin; Transfection; Wortmannin