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.
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 humanurothelial 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.
Authors: Keiichiro Mori; Takafumi Yanagisawa; Satoshi Katayama; Ekaterina Laukhtina; Benjamin Pradere; Hadi Mostafaei; Fahad Quhal; Pawel Rajwa; Marco Moschini; Francesco Soria; David D'andrea; Mohammad Abufaraj; Simone Albisinni; Wojciech Krajewski; Wataru Fukuokaya; Jun Miki; Takahiro Kimura; Shin Egawa; Jeremy Yc Teoh; Shahrokh F Shariat Journal: World J Urol Date: 2022-08-13 Impact factor: 3.661