BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect.
Nat Med
; 9(8): 1033-8, 2003 Aug.
Article
em En
| MEDLINE
| ID: mdl-12872164
ABSTRACT
The mechanisms of retinoid activity in tumors remain largely unknown. Here we establish that retinoids cause extensive apoptosis of medulloblastoma cells. In a xenograft model, retinoids largely abrogated tumor growth. Using receptor-specific retinoid agonists, we defined a subset of mRNAs that were induced by all active retinoids in retinoid-sensitive cell lines. We also identified bone morphogenetic protein-2 (BMP-2) as a candidate mediator of retinoid activity. BMP-2 protein induced medulloblastoma cell apoptosis, whereas the BMP-2 antagonist noggin blocked both retinoid and BMP-2-induced apoptosis. BMP-2 also induced p38 mitogen-activated protein kinase (MAPK), which is necessary for BMP-2- and retinoid-induced apoptosis. Retinoid-resistant medulloblastoma cells underwent apoptosis when treated with BMP-2 or when cultured with retinoid-sensitive medulloblastoma cells. Retinoid-induced expression of BMP-2 is thus necessary and sufficient for apoptosis of retinoid-responsive cells, and expression of BMP-2 by retinoid-sensitive cells is sufficient to induce apoptosis in surrounding retinoid-resistant cells.
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Base de dados:
MEDLINE
Assunto principal:
Retinoides
/
Neoplasias Encefálicas
/
Fator de Crescimento Transformador beta
/
Apoptose
/
Proteínas Morfogenéticas Ósseas
/
Comunicação Parácrina
/
Meduloblastoma
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos