Table 1.
Figure 1: GR mRNA isoform levels | Resistant cells have higher expression of GR isoforms 1C and 1D, and lower expression of isoform 1F than sensitive cells in basal conditions. |
Dexamethasone-treatment downregulated 5′UTR mRNA isoform 1C and 3′UTR mRNA isoform α in resistant cells only. | |
Figure 2: Effect of GR-1Cα Overexpression |
GR-1Cα overexpression in resistant cells did not improve in vitro response to dexamethasone as determined by NOS3 downregulation, SERPINE1 upregulation, and decreases in aPTT. |
GR-1Cα overexpression further downregulated the expression of 5′UTR mRNA isoforms 1B (in resistant cells only) and 1H in both sensitivity groups. | |
Figure 3: GR promoter activity | There were no significant differences in basal GR promoter (unmethylated) activity between sensitive and resistant cells. |
Dexamethasone treatment decreased promoter 1F activity in both sensitivity groups, decreased promoter 1B activity in resistant cells only and increased promoter 1D activity in sensitive cells only. | |
Promoter activity differences between sensitive and resistant cells did not correlate with differences in GR 5′UTR mRNA levels. | |
Figure 4: GR promoter methylation and AZA treatment |
Sensitive cells have higher promoter 1D methylation levels and lower promoter 1F and 1H methylation levels compared to resistant cells. |
Promoter methylation levels correlated with GR 5′UTR mRNA levels. | |
AZA treatment upregulated the expression of all GR mRNA isoforms except isoform 1D in resistant cells. | |
AZA treatment improved in vitro dexamethasone response in resistant cells as determined by NOS3 downregulation and SERPINE1 upregulation. | |