English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/8144
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

Overexpression of Akt converts radial growth melanoma to vertical growth melanoma

AutorGovindarajan, Baskaran; Sligh, James E.; Vincent, Bethaney J.; Li, Meiling; Canter, Jeffrey A.; Nickoloff, Brian J.; Rodenburg, Richard J.; Smeitink, Jan A.; Oberley, Larry; Zhang, Yuping; Slingerland, Joyce; Arnold, Rebecca S.; Lambeth, J. David; Cohen, Cynthia; Hilenski, Lu; Griendling, Kathy; Martínez-Díez, Marta; Cuezva, José M. ; Arbiser, Jack L.
Palabras claveMelanoma growth
Fecha de publicación22-feb-2007
EditorAmerican Society for Clinical Investigation
CitaciónJ. Clin. Invest. 117(3): 719-729 (2007)
ResumenMelanoma is the cancer with the highest increase in incidence, and transformation of radial growth to vertical growth (i.e., noninvasive to invasive) melanoma is required for invasive disease and metastasis. We have previously shown that p42/p44 MAP kinase is activated in radial growth melanoma, suggesting that further signaling events are required for vertical growth melanoma. The molecular events that accompany this transformation are not well understood. Akt, a signaling molecule downstream of PI3K, was introduced into the radial growth WM35 melanoma in order to test whether Akt overexpression is sufficient to accomplish this transformation. Overexpression of Akt led to upregulation of VEGF, increased production of superoxide ROS, and the switch to a more pronounced glycolytic metabolism. Subcutaneous implantation of WM35 cells overexpressing Akt led to rapidly growing tumors in vivo, while vector control cells did not form tumors. We demonstrated that Akt was associated with malignant transformation of melanoma through at least 2 mechanisms. First, Akt may stabilize cells with extensive mitochondrial DNA mutation, which can generate ROS. Second, Akt can induce expression of the ROS-generating enzyme NOX4. Akt thus serves as a molecular switch that increases angiogenesis and the generation of superoxide, fostering more aggressive tumor behavior. Targeting Akt and ROS may be of therapeutic importance in treatment of advanced melanoma
Versión del editorhttp://dx.doi.org/10.1172/JCI30102
URIhttp://hdl.handle.net/10261/8144
DOI10.1172/JCI30102
ISSN0021-9738 (print)
1558-8238 (online)
Aparece en las colecciones: (CBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
BGovindarajan_JClinInvest_719.pdfMain text750,49 kBAdobe PDFVista previa
Visualizar/Abrir
BGovindarajan_JClinInvest_Supplmentary.pdf474,06 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.