Role of Akt in Tumorigenesis and Angiogenesis of MC-SV-HUC T2 Cell Line / 대한해부학회지

ABSTRACT

Protein Kinase B (PKB/Akt) is a serine/threonine kinase that plays important roles in multiple physiological and pathological processes. Specially, Akt activation induces tumorigenesis in many cancers. However, molecular mechanism related in tumorigenesis is unclear in urothelial cell carcinoma. This study investigated Akt functions in the tumorigenesis and angiogenesis of tumorigenic human urothelial cell line, MC-SV-HUC T2. For this study, stable clonal cells were established by introducing myristrated Akt (Myr-Akt) or dominant-negative Akt (DNAkt) into MC-SV-HUC T2. As for the underlying mechanism, Western blot analysis for Akt and its related proteins and kinase activity assay were used. And BrdU incorporation and immunohistochemistry revealed cell proliferation and angiogenesis. DN-Akt expression decreased in vitro cell growth and proliferation. Akt inactivation decreased the phosphorylation of glycogen synthase kinase 3beta and retinoblastoma proteins and the expression of Cyclin D1 protein as well as cyclin dependent kinase 4 activity. A mouse xenograft model showed that DN-Akt overexpression reduced tumor growth and microvessel formation. Since these findings indicate that Akt is involved in a part of the mechanisms of tumorigenesis and angiogenesis, Akt may be useful as a target molecule for bladder cancer therapy.