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Updated: Aug 19, 2026
Three-Dimensional (3D) Tumor Spheroid Invasion Assay
Published on: May 1, 2015
Dickkopf-3/REIC functions as a suppressor gene of tumor growth
Sen-Yung Hsieh1, Pei-Shan Hsieh, Cheng-Tang Chiu
1Liver Research Unit, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. siming@adm.sgmh.org.tw
Abstract:
To identify putative tumor suppressor genes in hepatocarcinogenesis, we combined the representational difference analysis and reverse northern blot identifying downregulated genes in human hepatoma tissues. One of them was Dkk-3/REIC. Dkk-3/REIC was downregulated in 11 out of the 20 human hepatoma tissues as compared to their counterparts of noncancerous liver tissues by northern blot analysis. It was also downregulated in 29 out of 48 human cancer samples including the kidney, urinary bladder, prostate, pancreas and lung cancers. Its gene product, Dkk-3/REIC, was found to be N-glycosylated and have two isoforms, the 55 kDa in the cytosol and 50 kDa secreted in the medium. Ectopic expression of Dkk-3/REIC in HeLa, Hep3B and Huh 7 cells led to suppression of cell growth, which was primarily attributable to induction of cell apoptosis. The suppression phenomenon was found to be cell-type related (most prominent in HeLa and least in Hep3B cells) and cell-density dependent (attenuated as the cell density increased). Transduction of Dkk-3/REIC into HeLa and Hep3B cells caused suppression on colony formation in vitro and reduced tumor growth rate in inoculated athymic nude mice. In conclusion, these data indicate that Dkk-3/REIC functions as a suppressor for human tumor growth.
Insights
Dickkopf-3 (Dkk-3)/Reichert
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hepatocellular carcinoma (HCC) pathogenesis involves the identification of novel tumor suppressor genes.
- Downregulation of specific genes in cancerous tissues is a key indicator for potential tumor suppressors.
- Understanding gene expression changes is crucial for identifying therapeutic targets in cancer.
Purpose of the Study:
- To identify novel tumor suppressor genes involved in hepatocarcinogenesis.
- To investigate the role of Dickkopf-3 (Dkk-3)/Reichert (REIC) in human cancers.
- To elucidate the functional mechanism of Dkk-3/REIC as a potential tumor suppressor.
Main Methods:
- Representational difference analysis and reverse northern blot were used to identify downregulated genes in hepatoma tissues.
- Northern blot analysis was performed to confirm Dkk-3/REIC downregulation in various human cancer samples.
- Ectopic expression studies in cancer cell lines (HeLa, Hep3B, Huh 7) and in vivo tumor xenografts were conducted.
Main Results:
- Dkk-3/REIC was significantly downregulated in human hepatoma tissues and other cancer types (kidney, bladder, prostate, pancreas, lung).
- Ectopic expression of Dkk-3/REIC induced cell apoptosis and suppressed cell growth in a cell-type and cell-density dependent manner.
- Dkk-3/REIC expression reduced colony formation in vitro and inhibited tumor growth in athymic nude mice.
Conclusions:
- Dkk-3/REIC functions as a tumor suppressor gene.
- Dkk-3/REIC exhibits potent anti-proliferative and pro-apoptotic effects on cancer cells.
- Dkk-3/REIC represents a potential therapeutic target for human tumor treatment.
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