Growth and differentiation factor 3 induces expression of genes related to differentiation in a model of cancer stem cells and protects them from retinoic acid-induced apoptosis.
PLoS One
; 8(8): e70612, 2013.
Article
en En
| MEDLINE
| ID: mdl-23950971
ABSTRACT
Misexpression of growth factors, particularly those related to stem cell-like phenotype, is often observed in several cancer types. It has been found to influence parameters of disease progression like cell proliferation, differentiation, maintenance of undifferentiated phenotype and modulation of the immune system. GDF3 is a TGFB family member associated with pluripotency and differentiation during embryonic development that has been previously reported to be re-expressed in a number of cancer types. However, its role in tumor development and progression has not been clarified yet. In this study we decipher the role of GDF3 in an in vitro model of cancer stem cells, NCCIT cells. By classical approach to study protein function combined with high-throughput technique for transcriptome analysis and differentiation assays we evaluated GDF3 as a potential therapeutic target. We observed that GDF3 robustly induces a panel of genes related to differentiation, including several potent tumor suppressors, without impacting the proliferative capacity. Moreover, we report for the first time the protective effect of GDF3 against retinoic acid-induced apoptosis in cells with stem cell-like properties. Our study implies that blocking of GDF3 combined with retinoic acid-treatment of solid cancers is a compelling direction for further investigations, which can lead to re-design of cancer differentiation therapies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tretinoina
/
Células Madre Neoplásicas
/
Diferenciación Celular
/
Regulación de la Expresión Génica
/
Apoptosis
/
Factor 3 de Diferenciación de Crecimiento
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania