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Inhibitory effect of testosterone on gap junctional intercellular communication of human transitional cell carcinoma
1Department of Urology, School of Medicine, Tokyo Medical and Dental University, Japan.
Abstract:
A dye transfer method was applied to investigate the effect of testosterone on gap junctional intercellular communication (IC) of two kinds of human transitional cell carcinoma cell lines, JTC-30 and JTC-32. When JTC-30 cells were cultured with testosterone at nontoxic concentrations (17-69 microM), a dose and time dependent inhibition of dye transfer was observed. More than 90% inhibition occurred after exposure to 69 microM testosterone for 96 h. The inhibition was reversed rapidly after testosterone deprivation. Similar results were obtained with JTC-32 cells. 17 beta-Estradiol showed no inhibitory effect on IC of both transitional cell carcinoma cell lines even at toxic levels. Testosterone exhibited no inhibitory effect on IC of human fibroblasts. The inhibitory effect of 5 alpha-dihydrotestosterone was almost similar to that of testosterone. At concentrations examined, cyproterone acetate influenced neither dye transfer nor the inhibitory effect of testosterone, suggesting a mechanism of testosterone action different from that of the known receptor system. Since blockage of IC has been indicated as one reliable evidence for tumor promotion, current results suggest that testosterone is a possible endogenous promoter of the bladder carcinoma and may therefore possibly play a role on the sexually different incidence of bladder carcinoma.
Insights
Testosterone inhibits gap junctional intercellular communication (IC) in bladder cancer cells, suggesting it may promote tumor growth. This effect was dose-dependent and reversible, unlike estrogen or testosterone
Area of Science:
- Oncology
- Endocrinology
- Cell Biology
Background:
- Gap junctional intercellular communication (IC) is crucial for normal cell function.
- Bladder carcinoma exhibits a higher incidence in males, suggesting hormonal influences.
Purpose of the Study:
- To investigate the effect of testosterone on IC in human transitional cell carcinoma cell lines.
- To explore the potential role of testosterone as an endogenous promoter of bladder carcinoma.
Main Methods:
- Dye transfer method used to assess IC in JTC-30 and JTC-32 cell lines.
- Cells were exposed to varying concentrations and durations of testosterone, 17 beta-estradiol, and 5 alpha-dihydrotestosterone.
Main Results:
- Testosterone significantly inhibited IC in a dose- and time-dependent manner in both cell lines.
- Inhibition was rapidly reversible upon testosterone removal.
- 17 beta-estradiol and testosterone had no effect on human fibroblast IC.
- 5 alpha-dihydrotestosterone showed a similar inhibitory effect to testosterone.
Conclusions:
- Testosterone acts as an endogenous promoter of bladder carcinoma by inhibiting IC.
- The mechanism of testosterone's action appears independent of known receptor systems.
- Testosterone may contribute to the sex-based differences in bladder carcinoma incidence.