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Updated: May 2, 2026

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
TR4 nuclear receptor functions as a tumor suppressor for prostate tumorigenesis via modulation of DNA damage/repair
Shin-Jen Lin, Soo Ok Lee, Yi-Fen Lee
1chang@urmc.rochester.edu.
Abstract:
Testicular nuclear receptor 4 (TR4), a member of the nuclear receptor superfamily, plays important roles in metabolism, fertility and aging. The linkage of TR4 functions in cancer progression, however, remains unclear. Using three different mouse models, we found TR4 could prevent or delay prostate cancer (PCa)/prostatic intraepithelial neoplasia development. Knocking down TR4 in human RWPE1 and mouse mPrE normal prostate cells promoted tumorigenesis under carcinogen challenge, suggesting TR4 may play a suppressor role in PCa initiation. Mechanism dissection in both in vitro cell lines and in vivo mice studies found that knocking down TR4 led to increased DNA damage with altered DNA repair system that involved the modulation of ATM expression at the transcriptional level, and addition of ATM partially interrupted the TR4 small interfering RNA-induced tumorigenesis in cell transformation assays. Immunohistochemical staining in human PCa tissue microarrays revealed ATM expression is highly correlated with TR4 expression. Together, these results suggest TR4 may function as a tumor suppressor to prevent or delay prostate tumorigenesis via regulating ATM expression at the transcriptional level.
Insights
Testicular nuclear receptor 4 (TR4) acts as a tumor suppressor, preventing prostate cancer development by regulating DNA repair and ATM expression. This finding offers new insights into prostate cancer initiation and potential therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Testicular nuclear receptor 4 (TR4) is a nuclear receptor superfamily member involved in metabolism, fertility, and aging.
- The role of TR4 in cancer progression, particularly prostate cancer (PCa), is not well understood.
Purpose of the Study:
- To investigate the function of TR4 in prostate cancer initiation and progression.
- To elucidate the molecular mechanisms underlying TR4's role in prostate tumorigenesis.
Main Methods:
- Utilized three mouse models and in vitro cell line studies (human RWPE1, mouse mPrE).
- Investigated the effects of TR4 knockdown on tumorigenesis, DNA damage, and DNA repair pathways.
- Examined the role of ATM expression modulation and its correlation with TR4 in prostate cancer.
- Performed immunohistochemical staining on human PCa tissue microarrays.
Main Results:
- TR4 prevents or delays prostate cancer/prostatic intraepithelial neoplasia development in mouse models.
- Knocking down TR4 in normal prostate cells promotes tumorigenesis and increases DNA damage.
- TR4 knockdown alters the DNA repair system through modulation of ATM expression at the transcriptional level.
- ATM expression is highly correlated with TR4 expression in human PCa tissues.
Conclusions:
- TR4 functions as a tumor suppressor in prostate cancer initiation.
- TR4 delays prostate tumorigenesis by regulating ATM expression and DNA repair pathways.
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