Related Experiment Video
Updated: Aug 8, 2026
Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus (KSHV)
Published on: September 15, 2010
Identification of PDZK4, a novel human gene with PDZ domains, that is upregulated in synovial sarcomas
Satoshi Nagayama1, Megumi Iiizumi, Toyomasa Katagiri
1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Abstract:
In an earlier study designed to investigate molecular mechanisms of carcinogenesis in synovial sarcomas (SSs), we applied a cDNA microarray to detect human genes with significantly increased expression in SS cells. Among the genes selected in this way, we identified a novel transcript, subsequently designated PDZK4 (PDZ domain-containing 4), that was specifically upregulated in all of the 13 SS cases we examined. On Northern blots of normal human tissues, the PDZK4 transcript was expressed only in fetal brain. Immunocytochemical staining of transfected COS7 cells showed that the PDZK4 gene product localized mainly under the plasma membrane. Treatment of human SS cells with small interfering RNA (siRNA) inhibited the expression of PDZK4 and resulted in the suppression of tumor-cell growth. Induction of exogenous PDZK4 expression promoted growth of T98G and COS7 cells in which no endogenous expression of PDZK4 was observed. Taken together, these findings strongly suggest that inappropriate expression of PDZK4 might play an important role in the proliferation of SS cells and that the gene might be a suitable molecular target for designing of novel drugs to treat SS patients.
Insights
Researchers identified PDZK4 (PDZ domain-containing 4) as a novel gene upregulated in synovial sarcoma. Inhibiting PDZK4 suppressed tumor cell growth, suggesting it as a potential therapeutic target for synovial sarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Synovial sarcomas (SSs) are rare soft tissue tumors with poorly understood molecular mechanisms of carcinogenesis.
- Previous studies aimed to identify genes involved in SS development.
Purpose of the Study:
- To identify novel genes overexpressed in synovial sarcoma.
- To investigate the role of the identified gene, PDZK4 (PDZ domain-containing 4), in SS cell proliferation.
- To evaluate PDZK4 as a potential therapeutic target for synovial sarcoma.
Main Methods:
- cDNA microarray analysis to detect differentially expressed genes in SS cells.
- Northern blotting to assess PDZK4 transcript expression in normal human tissues.
- Immunocytochemistry to determine the subcellular localization of the PDZK4 protein.
- Small interfering RNA (siRNA) to inhibit PDZK4 expression in SS cells.
- Functional assays to assess the impact of PDZK4 modulation on cell growth.
Main Results:
- A novel transcript, PDZK4, was specifically upregulated in all 13 examined SS cases.
- PDZK4 transcript was detected only in fetal brain among normal human tissues.
- The PDZK4 gene product localized primarily beneath the plasma membrane.
- siRNA-mediated inhibition of PDZK4 suppressed synovial sarcoma cell growth.
- Exogenous PDZK4 expression promoted the growth of T98G and COS7 cells.
Conclusions:
- Inappropriate PDZK4 expression is strongly implicated in the proliferation of synovial sarcoma cells.
- PDZK4 represents a promising molecular target for the development of novel therapeutic strategies for synovial sarcoma.
Related Concept Videos
02:23Abnormal Proliferation
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:22PI3K/mTOR/AKT Signaling Pathway
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...