Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors.
Oncogene
; 26(39): 5762-71, 2007 Aug 23.
Article
en En
| MEDLINE
| ID: mdl-17384686
ABSTRACT
Galanin receptor 1 (GALR1) maps to a common region of 18q loss in head and neck squamous cell carcinomas and is frequently inactivated by methylation. To investigate effects of GALR1 and its signaling pathways, we stably expressed hemaglutinin-tagged GALR1 in a human oral carcinoma cell line (UM-SCC-1-GALR1) that expresses no endogenous GALR1. In transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2 (ERK1/2) and suppressed proliferation. Galanin stimulation mediated decreased expression of cyclin D1 and increased expression of the cyclin-dependent kinase inhibitors (CKI), p27(Kip1) and p57(Kip2). Pretreatment with the ERK1/2-specific inhibitor U0126 prevented these galanin-induced effects. Phosphatidylinositol 3-kinase (PI3K) pathway activation did not differ in UM-SCC-1-GALR1 and UM-SCC-1-mock cells after galanin treatment. Pertussis toxin and LY294002 inhibition demonstrated that galanin and GALR1 induce ERK1/2 activation via Galphai, not the PI3K pathway-linked to the Gbetagamma subunit. Galanin and GALR1 also inhibit colony formation and tumor growth in vivo. Our results implicate GALR1, a Gi protein-coupled receptor, as a tumor suppressor gene that inhibits cell proliferation via ERK1/2 activation.
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Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Escamosas
/
Galanina
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Proteína Quinasa 1 Activada por Mitógenos
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Receptor de Galanina Tipo 1
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Proteína Quinasa 3 Activada por Mitógenos
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Proliferación Celular
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Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina
Límite:
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos