Overexpression of thymosin beta4 increases pseudopodia formation in LNCaP prostate cancer cells.
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.
Ito
Mai
M
Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Iguchi
Kazuhiro
K
Usui
Shigeyuki
S
Hirano
Kazuyuki
K
D000730:Androstadienes / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D008297:Male; D008858:Microscopy, Phase-Contrast; D009570:Nitriles / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011554:Pseudopodia / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology; D013947:Thymosin / Q000096:biosynthesis*; D014162:Transfection; D000077191:Wortmannin; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors; D000099201:Thymosin beta(4)
D000730:Androstadienes; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002070:Butadienes; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020123:Sirolimus; D013947:Thymosin; D000077191:Wortmannin; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000099201:Thymosin beta(4); C107953:RAC1 protein, human; C113580:U 0126; C031815:toxB protein, Clostridium difficile