Korean J Anat.  2008 Jun;41(2):111-119.

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

• Kim MK

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.

Keyword

Akt; Tumorigenesis; Urothelial cell carcinoma; Cell proliferation; Angiogenesis

MeSH Terms

Animals
Blotting, Western
Bromodeoxyuridine
Cell Line
Cell Proliferation
Cell Transformation, Neoplastic
Cyclin D1
Cyclin-Dependent Kinase 4
Glycogen Synthase Kinases
Humans
Immunohistochemistry
Mice
Microvessels
Pathologic Processes
Phosphorylation
Phosphotransferases
Proteins
Proto-Oncogene Proteins c-akt
Retinoblastoma Protein
Staphylococcal Protein A
Transplantation, Heterologous
Urinary Bladder Neoplasms
Bromodeoxyuridine
Cyclin D1
Cyclin-Dependent Kinase 4
Glycogen Synthase Kinases
Phosphotransferases
Proteins
Proto-Oncogene Proteins c-akt
Retinoblastoma Protein
Staphylococcal Protein A