Cellular FLIP(L) plays a survival role and regulates morphogenesis in breast epithelial cells.
Biochim Biophys Acta
; 1813(1): 168-78, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-20951169
ABSTRACT
Strong evidences support the inhibitory activity of cellular FLICE-inhibitory protein (FLIP) in the apoptotic signalling by death receptors in tumor cells. However, little is known about the role of FLIP in the regulation of apoptosis in non-transformed cells. In this report, we demonstrate that FLIP(L) plays an important role as a survival protein in non-transformed breast epithelial cells. Silencing of FLIP(L) by siRNA methodology enhances TRAIL-R2 expression and activates a caspase-dependent cell death process in breast epithelial cells. This cell death requires the expression of TRAIL, TRAIL-R2, FADD and procaspase-8 proteins. A mitochondria-operated apoptotic pathway is partially required for FLIP(L) siRNA-induced apoptosis. Interestingly, FLIP(L) silencing markedly abrogates formation of acinus-like structures in a three-dimensional basement membrane culture model (3D) of the human mammary MCF-10A cell line through a caspase-8 dependent process. Furthermore, over-expression of FLIP(L) in MCF-10A cells delayed lumen formation in 3D cultures. Our results highlight the central role of FLIP in maintaining breast epithelial cell viability and suggest that the mechanisms regulating FLIP levels should be finely controlled to prevent unwanted cell demise.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Mama
/
Apoptose
/
Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD
/
Morfogênese
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Espanha