Ligand-activated interaction of PPARδ with c-Myc governs the tumorigenicity of breast cancer.
Int J Cancer
; 143(11): 2985-2996, 2018 12 01.
Article
en En
| MEDLINE
| ID: mdl-30204243
ABSTRACT
Peroxisome proliferator-activated receptor (PPAR) δ is a promising therapeutic target in metabolic and inflammatory disorders. However, its role in oncogenesis is controversial, and its therapeutic potential remains to be determined. In our study, we show that ligand-activated PPARδ forms a complex with the proto-oncogene product c-Myc. The interaction of PPARδ with c-Myc affected the transcriptional activity of c-Myc and the expression of its target genes. The PPARδ-dependent regulation of c-Myc activity was associated with decreased tumorigenicity in breast cancer cells. Administration of the PPARδ ligand GW501516 inhibited tumor growth in xenograft model mice bearing MDA-MB-231 cells stably expressing wild-type PPARδ, but not those expressing dominant-negative PPARδ, by interfering with c-Myc function through protein-protein interaction. Our results indicating that PPARδ forms an antitumorigenic complex with c-Myc in the presence of ligand suggest a potential role of PPARδ in breast cancer development.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tiazoles
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Neoplasias de la Mama
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Proteínas Proto-Oncogénicas c-myc
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PPAR delta
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Carcinogénesis
Límite:
Animals
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Humans
Idioma:
En
Revista:
Int J Cancer
Año:
2018
Tipo del documento:
Article
País de afiliación:
Corea del Sur