Protocadherin PCDH10, involved in tumor progression, is a frequent and early target of promoter hypermethylation in cervical cancer.
Genes Chromosomes Cancer
; 48(11): 983-92, 2009 Nov.
Article
en En
| MEDLINE
| ID: mdl-19681120
ABSTRACT
Cervical cancer (CC) is the second most common cancer in women. Currently, no tractable molecular-based therapeutic targets exist for patients with invasive CC and no predictive markers of risk assessment for progression of precancerous lesions are identified. New molecular insights into CC pathogenesis are urgently needed. Towards this goal, we first determined the copy number alterations of chromosome 4 and then examined the role of PCDH10 mapped to 4q28 as a candidate tumor suppressor gene. We identified monosomy 4 in 47% of 81 invasive CC studied by SNP array and found that 91% of 130 invasive CC harboring methylation in the promoter region of the PCDH10 gene. We then showed that aberrant promoter hypermethylation of PCDH10 is associated with downregulation of gene expression and cell lines exposed to demethylating agent resulted in profound reactivated gene expression. We also showed that the promoter methylation in the PCDH10 gene occurs at an earliest identifiable stage of low-grade squamous intraepithelial lesion. Our studies demonstrate that inactivation of PCDH10 may be a critical event in CC progression and form a potentially useful therapeutic target for CC.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cadherinas
/
Neoplasias del Cuello Uterino
/
Metilación de ADN
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Genes Chromosomes Cancer
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos