PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression.
Br J Cancer
; 109(8): 2199-206, 2013 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-24045667
ABSTRACT
BACKGROUND:
The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.METHODS:
To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.RESULTS:
Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).CONCLUSION:
The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Ribosómicas
/
Neoplasias Gástricas
/
Proteína p53 Supresora de Tumor
/
Proteínas Supresoras de Tumor
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Br J Cancer
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón