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Int J Cancer. 2018 Dec 1;143(11):2985-2996. doi: 10.1002/ijc.31864. Epub 2018 Oct 4.

Ligand-activated interaction of PPARδ with c-Myc governs the tumorigenicity of breast cancer.

Author information

1
Sanghuh College of Life Sciences, Konkuk University, Seoul, South Korea.
2
Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston.
3
Department of Nursing, Semyung University, Jechon, South Korea.

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.

KEYWORDS:

PPARδ; breast cancer; c-Myc; protein-protein interaction; tumorigenicity

PMID:
30204243
DOI:
10.1002/ijc.31864
[Indexed for MEDLINE]

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