Metabotropic glutamate receptor 1 mediates melanocyte transformation via transactivation of insulin-like growth factor 1 receptor.
Pigment Cell Melanoma Res
; 27(4): 621-9, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24628914
ABSTRACT
Our laboratory previously described the oncogenic properties of metabotropic glutamate receptor 1 (mGluR1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in mGluR1-mediated melanocytic tumorigenesis in vivo. In particular, we identified AKT2 being the predominant isoform contributing to the activation of AKT. Suppression of Grm1 or AKT2 using an inducible Tet-R siRNA system resulted in a 60 or 30% reduction, respectively, in in vivo tumorigenesis. We show that simultaneous downregulation of Grm1 plus AKT2 results in a reduction of approximately 80% in tumor volumes, suggesting that both mGluR1 and AKT2 contribute to the tumorigenic phenotype in vivo. The discrepancy between the mild in vitro transformation characteristics and the aggressive in vivo tumorigenic phenotypes of these stable mGluR1-melanocytic clones led us to investigate the possible involvement of other growth factors. Here, we highlight a potential crosstalk network between mGluR1 and tyrosine kinase, insulin-like growth factor 1 receptor (IGF-1R).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Transcricional
/
Transformação Celular Neoplásica
/
Receptor IGF Tipo 1
/
Receptores de Glutamato Metabotrópico
/
Melanócitos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pigment Cell Melanoma Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos