The effects of physiological estrogen concentration on the immune response of urothelial carcinoma cells to bacillus Calmette-Guérin. J Urol 2011 Jan;185(1):298-304
Date
11/16/2010Pubmed ID
21075400DOI
10.1016/j.juro.2010.09.004Scopus ID
2-s2.0-78650026299 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
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.
Author List
Guise AI, Chen F, Zhang G, See WAuthor
Amy Guise MD Associate Professor in the Urologic Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adjuvants, ImmunologicBCG Vaccine
Carcinoma, Transitional Cell
Estrogens
Humans
NF-kappa B
Tumor Cells, Cultured
Urologic Neoplasms