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Updated: Jul 10, 2026

Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
HRK inactivation associated with promoter methylation and LOH in prostate cancer
Tomonori Higuchi1, Mitsutoshi Nakamura, Keiji Shimada
1Department of Pathology, Nara Medical University School of Medicine, Nara, Japan.
Objectives:
Recent studies in selected human tumors have demonstrated reduced expression of HRK with hypermethylation. Because no similar study has been performed specifically in prostatic lesions, we examined whether the methylation status of HRK is altered in prostate cancers.
Methods:
We chose to analyze the hypermethylation status of HRK, the expression of HRK protein and mRNA with 12q13.1 loss of heterozygosity (LOH) and with p53 mutation, and lesion apoptotic indices as determined by transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end-labeling (TUNEL) assays in 53 prostate cancers.
Results:
Twenty of the 53 prostate cancers (38%) demonstrated hypermethylation in either the promoter or in exon 1 and, more significantly, the loss of HRK expression observed in 14 cancers by immunohistochemistry (IHC) was associated with promoter methylation. In addition, high apoptotic indices in tumors were related to positive HRK expression. Prostate cancers demonstrating HRK methylation also showed methylation of multiple other genes, such as p14(ARF), p16(INK4a), O(6)-MGMT, and GTS-P, but, with the exception of one case, p53 mutations were not detected. When compared to tumors having a Gleason score (GS) of 5-6, a significant difference in the apoptotic indices was found among prostate cancers of GS 7 (P < 0.001) or GS 8-9 (P = 0.007). We also detected a close correlation between the loss of HRK expression and decreased apoptosis in GS 5-6 and GS 7 tumors (P = 0.008, P < 0.001, respectively).
Conclusions:
HRK appears to be inactivated principally by promoter hypermethylation in prostate cancers. We further suggest that the decreased expression of HRK may play an important role in tumor progression by modulating apoptotic cell death.
Insights
HRK gene promoter hypermethylation inactivates HRK in prostate cancer, leading to reduced expression and potentially promoting tumor progression by affecting apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Reduced expression of the HRK gene has been observed in certain human tumors due to hypermethylation.
- Prostate cancer research has not yet extensively investigated the methylation status of the HRK gene.
Purpose of the Study:
- To investigate the methylation status of the HRK gene in prostate cancer.
- To determine if HRK gene alterations correlate with other molecular changes and tumor characteristics.
Main Methods:
- Analysis of HRK gene promoter hypermethylation and HRK protein/mRNA expression in 53 prostate cancer samples.
- Assessment of 12q13.1 loss of heterozygosity (LOH), p53 mutations, and apoptotic indices using TUNEL assays.
- Evaluation of methylation status for other genes including p14(ARF), p16(INK4a), O(6)-MGMT, and GTS-P.
Main Results:
- 38% of prostate cancers exhibited HRK promoter or exon 1 hypermethylation.
- Loss of HRK expression, detected in 14 cancers, was significantly associated with promoter methylation.
- High apoptotic indices correlated with positive HRK expression, while HRK loss correlated with decreased apoptosis, particularly in lower Gleason scores.
Conclusions:
- HRK gene inactivation in prostate cancer primarily occurs through promoter hypermethylation.
- Decreased HRK expression may contribute to prostate cancer progression by influencing apoptotic cell death.
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