Peroxisome proliferator-activated receptor gamma inhibits cell growth and negatively regulates DNA methyltransferase promoter activity in SK-N-AS neuroblastoma cells

Abstract

Neuroblastoma is the most common extra-cranial childhood solid tumour which arises from embryonic neural crest cells that fail to undergo a differentiation programme to form mature sympathetic neurones. Most children with advanced stage neuroblastoma have a 5-year event free survival rate of only 20%. However, the spontaneous differentiation of some early stage neuroblastoma into non-malignant gangliomas has prompted the search for agents that can induce neuroblastoma differentiation. Peroxisome proliferator-activated receptor gamma (PPAR?) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors which play a major role in adipocyte differentiation and exhibits anticancer activity against a range of tumour cells in vitro. High levels of PPAR? have been shown to be associated with differentiated neuroblastoma and low levels of PPAR? with poorly differentiated tumours. Therefore, the aim of this project is to investigate whether PPAR? acts as a tumour suppressor gene in neuroblastoma. Our research shows that overexpression of PPAR? in the human neuroblastoma cell line SK-N-AS cells inhibited cell growth but had no effect on cell viability or the degree of differentiation, suggesting that PPAR? may modulate cell cycle progression in SK-N-AS neuroblastoma cells. Additionally, we show that PPAR? strongly represses the DNMT1 promoter activity. This suggests that PPAR? may in addition to regulating the cell cycle also modulate epigenetic processes within the cell.

More information

Identifiers

ORCID for Karen Lillycrop: orcid.org/0000-0001-7350-5489

Catalogue record

Export record