Stimulation of ATF3 interaction with Smad4 via TGF-ß1 for matrix metalloproteinase 13 gene activation in human breast cancer cells.
Int J Biol Macromol
; 134: 954-961, 2019 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-31082421
ABSTRACT
We previously reported that transforming growth factor-ß1 (TGF-ß1) stimulated the sustained and prolonged expression of activating transcription factor 3 (ATF3) in highly metastatic and invasive human breast cancer cells (MDA-MB231), in contrast to normal human mammary epithelial cells. However, the mechanism behind the stability of ATF3 expression is not yet known. Based on an in silico approach with co-immunoprecipitation and mass spectrometric analyses, we identified a number of proteins, including Smad4, that interacted with ATF3 after TGF-ß1 treatment in MDA-MB231 cells. The knockdown of Smad4 using the siRNA technique resulted in a significant loss of ATF3 expression in these cells. Chromatin immunoprecipitation was then used to identify the formation of an ATF3 and Smad4 complex at the matrix metalloproteinase 13 (MMP13) promoter upon TGF-ß1-treatment, and the knockdown of Smad4 decreased MMP13 promoter activity in MDA-MB231 cells. Our findings indicate that Smad4 is a pre-requisite for providing stability to ATF3 via TGF-ß1 in human breast cancer cells. The targeting of Smad4 may thus provide the sustainable loss of ATF3 expression that is needed to control breast cancer progression.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Ativação Transcricional
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Proteína Smad4
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Fator 3 Ativador da Transcrição
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Metaloproteinase 13 da Matriz
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Int J Biol Macromol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia