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Updated: May 14, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Castration therapy results in decreased Ku70 levels in prostate cancer
Firas L T Al-Ubaidi1, Niklas Schultz, Olga Loseva
1Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Purpose:
Neoadjuvant castration improves response to radiotherapy of prostate cancer. Here, we determine whether castration therapy impairs nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks (DSB) by downregulating Ku70 protein expression.
Experimental Design:
Twenty patients with locally advanced prostate cancer were enrolled, and 6 to 12 needle core biopsy specimens were taken from the prostate of each patient before treatment. Bilateral orchidectomy was conducted in eight patients and 12 patients were treated with a GnRH agonist. After castration, two to four similar biopsies were obtained, and the levels of Ku70 and γ-H2AX foci were determined by immunofluorescence in verified cancer tissues.
Results:
We observed that the androgen receptor binds directly to Ku70 in prostate tissue. We also found a reduction of the Ku70 protein levels in the cell nuclei in 12 of 14 patients (P < 0.001) after castration. The reduction in Ku70 expression correlated significantly with decreased serum prostate-specific antigen (PSA) levels after castration, suggesting that androgen receptor activity regulates Ku70 protein levels in prostate cancer tissue. Furthermore, a significant correlation between the reductions of Ku70 after castration versus changes induced of castration of γ-H2AX foci could be seen implicating a functional linkage of decreased Ku70 levels and impaired DNA repair.
Conclusions:
Castration therapy results in decreased levels of the Ku70 protein in prostate cancer cells. Because the Ku70 protein is essential for the NHEJ repair of DSBs and its downregulation impairs DNA repair, this offers a possible explanation for the increased radiosensitivity of prostate cancer cells following castration.
Insights
Castration therapy reduces Ku70 protein levels in prostate cancer cells, impairing DNA repair. This explains increased radiosensitivity following neoadjuvant castration for prostate cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neoadjuvant castration enhances prostate cancer radiotherapy response.
- Nonhomologous end-joining (NHEJ) is crucial for repairing DNA double-strand breaks (DSB).
Purpose of the Study:
- To investigate if castration therapy downregulates Ku70 protein expression.
- To determine if reduced Ku70 impairs NHEJ DNA repair in prostate cancer.
Main Methods:
- Biopsy samples from 20 prostate cancer patients before and after castration (orchidectomy or GnRH agonist).
- Immunofluorescence analysis of Ku70 and γ-H2AX foci in cancer tissues.
- Correlation analysis with serum prostate-specific antigen (PSA) levels.
Main Results:
- Androgen receptor directly binds to Ku70 in prostate tissue.
- Castration significantly reduced Ku70 nuclear levels in 12/14 patients (P < 0.001).
- Reduced Ku70 correlated with decreased PSA and impaired γ-H2AX foci, indicating functional linkage to DNA repair.
Conclusions:
- Castration therapy decreases Ku70 protein levels in prostate cancer cells.
- Ku70 downregulation impairs NHEJ DNA repair.
- This mechanism may explain enhanced prostate cancer radiosensitivity after castration.
