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Role of HNF4α in regulation of cell proliferation and drug response
Thesis (Dissertationen, Habilitationen)
ID 4627654
Author Heinzer, Julia
Author at UniBasel Meyer zu Schwabedissen, Henriette
Year 2016
Title Role of HNF4α in regulation of cell proliferation and drug response
Type of Thesis Masterarbeit
Start of thesis 11.01.2016
End of thesis 03.06.2016
Name of University University of Basel
Name of Faculty Philosophisch-Naturwissenschaftliche Fakultšt
Supervisor(s) / Fachvertreter/in Meyer zu Schwabedissen, Henriette

Mammalian nuclear receptors are a superfamily of highly conserved transcription factors that affect diverse biological functions, including carbohydrate and lipid metabo-lism, due to their regulation of the expression of various target genes. Nuclear receptors are commonly known to regulate various metabolizing enzymes and transporters which may lead to an altered regulation of drug response. One of member of this family is the orphan hepatocyte nuclear factor 4α (HNF4α), which has been associated with metabol-ic and cancerous diseases. This transcription factor is suggested to act as tumor suppres-sor and to inhibit cell proliferation.
In this work we studied the impact of HNF4α on cell proliferation by counting cells using a capillary based resistance measurement method after a fixed period of time and we confirmed the antiproliferative effect of HNF4α in HeLa and Caki-1 cells. Further-more, we investigated potential target genes of HNF4α such as cell cycle regulators by quantitative real-time PCR and identified the transcription factor NFκB1 as a potential target gene. Further investigation of the interaction between HNF4α and NFκB1 is not part of this work. Additionally, we tested if one of the pharmaceutical compounds – canreonic acid, chenodeoxycholic acid, chlorambucil, myristic acid or myristoleic acid – is able to affect the nuclear receptor HNF4α using a cell based dual reporter gene sys-tem. We have found that none of these compounds is able to regulate the activity of HNF4α.

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