Analysis of ARNT-responsive regions in the 5′-flanking region of
the COX-2 gene. A, luciferase vectors bearing various
lengths of the COX-2 gene promoter were constructed as indicated.
Site-directed mutagenesis of CRE consensus sequences in the 5′-flanking
region ranging from –57 to –53 bp of the COX-2 gene was
performed. The potential consensus sequences in the 5′-flanking region
are indicated. Plasmid transfection was performed as described under
“Experimental Procedures.” The luciferase activities and protein
concentrations were then determined and normalized. The expression ratios of
ARNT (1 μg)-treated cells to control cells are indicated. Results are
expressed as means ± S.E. of three independent experiments in
triplicate wells for each construct. B, cells were transfected with
pXC918, pXC918 CREm, and ARNT expression vector by lipofection. The luciferase
activities and protein concentrations were then determined and normalized.
Values represent means ± S.E. of three determinations. C,
cells were transfected with pXC918 by lipofection. After EGF or
CoCl2 treatment for 6 h, the luciferase activities and protein
concentrations were determined and normalized. Values represent means ±
S.E. of three determinations. Expressions of HIF-1α, COX-2, and c-Jun
proteins were analyzed by Western blot analysis using antibodies against
HIF-1α, COX-2, and c-Jun, respectively. D, SiHa cells were
transfected with pXC918 and ARNT siRNA oligonucleotides by lipofection. After
EGF or CoCl2 treatment for 6 h, the luciferase activities and
protein concentrations were determined and normalized. Values represent means
± S.E. of three determinations. Expressions of ARNT, COX-2, and
β-actin proteins were analyzed by Western blot analysis using antibodies
against ARNT, COX-2, and β-actin, respectively. E, OEC-M1 cells
were transfected with ARNT siRNA oligonucleotides by lipofection. After EGF
treatment for 6 h, the expression of ARNT, COX-2, c-Jun, EGFR, and
β-actin was analyzed by Western blot analysis. The relative density of
COX-2 protein was quantified as indicated.