The Journal of urology · 2011
The effects of physiological estrogen concentration on the immune response of urothelial carcinoma cells to bacillus Calmette-Guérin.
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Guise Amy I, Chen Fanghong, Zhang Guangjian, See William
Аннотация
PURPOSE: Meta-analysis has shown that bacillus Calmette-Guérin is less effective in females undergoing treatment for urothelial carcinoma. Urothelial carcinoma cells express immune regulatory proteins as a consequence of bacillus Calmette-Guérin induced, nuclear factor κB signaling. Nuclear factor κB is influenced by estrogen receptor binding. We evaluated the effect of the physiological estradiol concentration on the expression of bacillus Calmette-Guérin induced, nuclear factor κB regulated immune proteins.
MATERIALS AND METHODS: We determined the estrogen receptor expression status of human urothelial carcinoma cell lines by reverse transcriptase-polymerase chain reaction. The functional status of estrogen receptor signaling was established using estrogen receptor reporter constructs. We used gene expression profiling of urothelial carcinoma cells combined with reverse transcriptase-polymerase chain reaction to identify the nuclear factor κB dependent immune regulatory proteins expressed in response to bacillus Calmette-Guérin. We determined the influence of the estradiol concentration on bacillus Calmette-Guérin dependent interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 gene expression by quantitative reverse transcriptase-polymerase chain reaction.
RESULTS: Urothelial carcinoma cell lines expressed functional estrogen receptor. Nuclear factor κB signaling was inhibited by estradiol in a dose and estrogen receptor dependent manner. Urothelial carcinoma cell expression of interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 was up-regulated in response to bacillus Calmette-Guérin in a nuclear factor κB dependent manner. There was a significant dose dependent effect of estradiol on the expression of these genes in bacillus Calmette-Guérin treated urothelial carcinoma cells.
CONCLUSIONS: The physiological concentration of estrogen influences nuclear factor κB signaling and bacillus Calmette-Guérin dependent gene expression. Serum estradiol fluctuations in women may influence the response of urothelial carcinoma to intravesical bacillus Calmette-Guérin treatment.
MATERIALS AND METHODS: We determined the estrogen receptor expression status of human urothelial carcinoma cell lines by reverse transcriptase-polymerase chain reaction. The functional status of estrogen receptor signaling was established using estrogen receptor reporter constructs. We used gene expression profiling of urothelial carcinoma cells combined with reverse transcriptase-polymerase chain reaction to identify the nuclear factor κB dependent immune regulatory proteins expressed in response to bacillus Calmette-Guérin. We determined the influence of the estradiol concentration on bacillus Calmette-Guérin dependent interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 gene expression by quantitative reverse transcriptase-polymerase chain reaction.
RESULTS: Urothelial carcinoma cell lines expressed functional estrogen receptor. Nuclear factor κB signaling was inhibited by estradiol in a dose and estrogen receptor dependent manner. Urothelial carcinoma cell expression of interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 was up-regulated in response to bacillus Calmette-Guérin in a nuclear factor κB dependent manner. There was a significant dose dependent effect of estradiol on the expression of these genes in bacillus Calmette-Guérin treated urothelial carcinoma cells.
CONCLUSIONS: The physiological concentration of estrogen influences nuclear factor κB signaling and bacillus Calmette-Guérin dependent gene expression. Serum estradiol fluctuations in women may influence the response of urothelial carcinoma to intravesical bacillus Calmette-Guérin treatment.