MTA1 promotes cell proliferation via DNA damage repair in epithelial ovarian cancer.
Genet Mol Res
; 13(4): 10269-78, 2014 Dec 04.
Article
em En
| MEDLINE
| ID: mdl-25501238
ABSTRACT
We examined whether metastasis-associated gene 1 (MTA1) promotes cell proliferation via DNA damage repair in ovarian cancer. MTA1 was successfully down-regulated using small interfering RNA in the epithelial ovarian cancer cell lines SKOV-3 and OVCAR-3. Cell growth was evaluated through MTT and colony formation assays. Fluorescence-activated cell sorting analysis was used to evaluate the distribution of cells in the cell cycle, and cytotoxicity assays were performed to study cell sensitivity to cisplatin. A neutral comet assay was used to measure levels of ionizing radiation-induced DNA damage in SKOV-3 cells, and Western blot analyses were carried out to examine the expression of key proteins involved in DNA damage repair pathways. MTA1 knockdown markedly inhibited cell growth and led to S phase cell cycle arrest. In addition, MTA1 depletion conferred sensitivity of ovarian cancer cells to cisplatin. Moreover, MTA1 depletion increased the level of ionizing radiation-induced DNA damage and caused irreparable damage, which was illustrated by a remarkable increase and persistent existence of a comet tail as well as protein expression levels of γH2AX, pRPA, and pChk1, all of which play critical roles in DNA repair. Thus, MTA1 promotes the proliferation of epithelial ovarian cancer cells by enhancing DNA repair.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
/
Proteínas Repressoras
/
DNA de Neoplasias
/
Neoplasias Epiteliais e Glandulares
/
RNA Interferente Pequeno
/
Reparo do DNA
/
Histona Desacetilases
Limite:
Female
/
Humans
Idioma:
En
Revista:
Genet Mol Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China