| Registro completo |
| Provedor de dados: |
BJMBR
|
| País: |
Brazil
|
| Título: |
TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner
|
| Autores: |
Guo,S.-Y.
Shen,X.
Yang,J.
Yuan,J.
Yang,R.-L.
Mao,K.
Zhao,D.-H.
Li,C.-J.
|
| Data: |
2007-05-01
|
| Ano: |
2007
|
| Palavras-chave: |
Tissue inhibitor of metalloproteinases-1
Hepatocellular carcinoma
Interleukin-6
STAT3
P21
|
| Resumo: |
The tissue inhibitor of metalloproteinases (TIMP)-1 is a multifunctional protein which is not only an inhibitor of matrix metalloproteinases (MMPs) but also to have a possible "cytokine-like" action. Here, we first compared mRNA expression of TIMP-1 and MMP-9 in BEL-7402 (a hepatocellular carcinoma cell line), L-02 (a normal liver cell line) and QSG-7701 (a cell line derived from peripheral tissue of liver carcinoma) using real-time quantitative RT-PCR. By evaluating the variation of the MMP-9/TIMP-1 ratio as an index of reciprocal changes of the expression of the two genes, we observed that the MMP-9/TIMP-1 ratio was about 13- and 5-fold higher in BEL-7402 than in L-02 and QSG-7701, respectively. Significantly, overexpression of TIMP-1 decreased the MMP-9/TIMP-1 ratio in BEL-7402 and then inhibited the cell growth to 60% and reduced the migration to about 30%. Meanwhile, our data showed that interleukin-6 (IL-6) (100 ng/mL) could also inhibited the cell growth of BEL-7402. Further studies indicated that TIMP-1 mediated the inhibitory effect of IL-6 on BEL-7402 cell proliferation in a STAT3-dependent manner, which could further accelerate the expression of the cyclin-dependent kinase inhibitor p21. A dominant negative STAT3 mutant totally abolished IL-6-induced TIMP-1 expression and its biological functions. The present results demonstrate that TIMP-1 may be one of the mediators that regulate the inhibitory effect of IL-6 on BEL-7402 proliferation in which STAT3 signal transduction and p21 up-regulation also play important roles.
|
| Tipo: |
Info:eu-repo/semantics/article
|
| Idioma: |
Inglês
|
| Identificador: |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000500004
|
| Editor: |
Associação Brasileira de Divulgação Científica
|
| Relação: |
10.1590/S0100-879X2006005000084
|
| Formato: |
text/html
|
| Fonte: |
Brazilian Journal of Medical and Biological Research v.40 n.5 2007
|
| Direitos: |
info:eu-repo/semantics/openAccess
|
