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Published on: August 12, 2015
PRDM5 is silenced in human cancers and has growth suppressive activities
1The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract:
Several genes that contain the PR (PRDI-BF1 and RIZ) domain have been linked with human cancers. We describe here a new PR-domain-containing gene designated as PRDM5 (PFM2). A PRDM5 cDNA was isolated based on its homology to the PR domain of RIZ1 (PRDM2). The gene encodes an open reading frame of 630 amino acids and contains a PR domain in the NH-terminal region followed by 16 zinc finger motifs. Radiation hybrid analysis mapped PRDM5 to human chromosome 4q26, a region thought to harbor tumor suppressor genes for breast, ovarian, liver, lung, colon, and other cancers. The gene has a CpG island promoter and is silenced in human breast, ovarian, and liver cancers. A recombinant adenovirus expressing PRDM5 caused G2/M arrest and apoptosis upon infection of tumor cells. These results suggest that inactivation of PRDM5 may play a role in carcinogenesis.
Insights
Researchers identified a new gene, PRDM5, involved in cancer. Silenced in several cancers, its expression induced cell cycle arrest and apoptosis, suggesting PRDM5 acts as a tumor suppressor.
Area of Science:
- Genetics and Molecular Biology
- Cancer Research
- Human Genetics
Background:
- The PR (PRDI-BF1 and RIZ) domain is present in genes associated with human cancers.
- Tumor suppressor genes are often located on chromosome 4q26, a region implicated in various cancers.
Purpose of the Study:
- To identify and characterize a novel PR-domain-containing gene, PRDM5.
- To investigate the role of PRDM5 in human cancers, particularly its potential tumor suppressor function.
Main Methods:
- Isolation of PRDM5 cDNA based on homology to RIZ1 (PRDM2).
- Analysis of PRDM5 gene structure, including its open reading frame and zinc finger motifs.
- Radiation hybrid mapping to determine PRDM5 chromosomal location.
- Investigation of PRDM5 promoter methylation and gene silencing in cancer cell lines.
- Functional studies using recombinant adenovirus to express PRDM5 in tumor cells.
Main Results:
- PRDM5 encodes a 630-amino acid protein with an N-terminal PR domain and 16 zinc finger motifs.
- PRDM5 was mapped to human chromosome 4q26.
- PRDM5 exhibits a CpG island promoter and is silenced in breast, ovarian, and liver cancer cells.
- Expression of PRDM5 via adenovirus induced G2/M cell cycle arrest and apoptosis in tumor cells.
Conclusions:
- PRDM5 is a novel PR-domain-containing gene potentially functioning as a tumor suppressor.
- Inactivation or silencing of PRDM5 may contribute to the development of various human cancers.
- PRDM5 warrants further investigation for its role in carcinogenesis and potential therapeutic applications.
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