An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells.
Mol Cancer
; 10: 135, 2011 Nov 03.
Article
em En
| MEDLINE
| ID: mdl-22051041
ABSTRACT
BACKGROUND:
Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA) caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array-based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance.RESULTS:
Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR.CONCLUSION:
These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug-resistance is intricately controlled by genomic status, gene and miRNA expression changes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Regulação Neoplásica da Expressão Gênica
/
Resistencia a Medicamentos Antineoplásicos
/
MicroRNAs
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article