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Title: Peroxisome proliferator-activated receptor gamma inhibits cell growth and negatively regulates DNA methyltransferase promoter activity in SK-N-AS neuroblastoma cells
Author: Huang, Chih-Hua
ISNI:       0000 0004 2727 380X
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2012
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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 (PPARƴ) 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 PPARƴ have been shown to be associated with differentiated neuroblastoma and low levels of PPARƴ with poorly differentiated tumours. Therefore, the aim of this project is to investigate whether PPARƴ acts as a tumour suppressor gene in neuroblastoma. Our research shows that overexpression of PPARƴ 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 PPARƴ may modulate cell cycle progression in SK-N-AS neuroblastoma cells. Additionally, we show that PPARƴ strongly represses the DNMT1 promoter activity. This suggests that PPARƴ may in addition to regulating the cell cycle also modulate epigenetic processes within the cell.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available