The differential effects of all-trans retinoic acid on retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPARβ/δ)-dependent signaling in the human NGP neuroblastoma cancer cell line.

Open Access
Author:
Krevitz, Jacqueline Anne
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Jeffrey Maurice Peters, Thesis Supervisor
  • Stephen Wade Schaeffer, Honors Advisor
Keywords:
  • PPAR
  • neuroblastoma
  • ngp
  • retinoic acid
  • atra
  • rar
  • cancer
Abstract:
Although the roles of PPARα and PPARγ have been widely explored and agreed upon, the role of PPARβ/δ in carcinogenesis has been widely contested. atRA has been postulated to act on RARα or PPARβ/δ in a context-specific manner to cause differentiation and cell survival, respectively, depending on the ratio of FABP-II/CRABP5 protein. However, recent research has directly contested these results, and suggested atRA is not a ligand for PPARβ/δ, and that ligand activation of PPARβ/δ causes an arrest in cell growth. The purpose of this paper was to explore the effects of all-trans retinoic acid (atRA), GW0742, and DG172 on the nuclear receptors PPARβ/δ and RARα in atRA-sensitive neuroblastoma (NGP) cells. Western blot was used to confirm the presence of RARα, RXRα, and PPARβ/δ proteins in NGP cells. mRNA analysis using qPCR suggested that atRA acts through RARα, but not PPARβ/δ. Cell growth and cell count were measured through a cell proliferation assay. This showed that ligand activation of PPARβ/δ through GW0742-treated NGP cells significantly inhibited cell growth. Cell morphology was closely monitored over a period of 72 hours and suggested that atRA caused differentiation of NGP cells. This data suggests that atRA only acts through RARα to cause cell differentiation. In addition, it shows that ligand activation of PPARβ/δ inhibits cell survival. Taken together, these results refute the hypothesis that atRA acts in a context-specific manner to activate PPARβ/δ and induce cell survival.