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Updated: Aug 19, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Down-regulation of DMBT1 gene expression in human oral squamous cell carcinoma
Massao Alberto Imai1, Tetsuhiro Moriya, Fabiana Lica Imai
1Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Abstract:
Deleted in malignant brain tumors 1 (DMBT1) gene was recently isolated on chromosome 10q25.3-26.1 and has been proposed as a putative candidate tumor suppressor for brain, esophageal, gastric, colorectal, and lung cancer. However, little is known about the association of DMBT1 with oral squamous cell carcinoma (OSCC). To study the role of DMBT1 gene in OSCC oncogenesis, we examined 9 OSCC derived cell lines and 45 primary OSCC tissue specimens with respective normal tissues. Semi-quantitative reverse transcriptase chain reaction (RT-PCR) analysis revealed down-regulation or deletion of DMBT1 expression in all of the 9 cell lines and in 18 (40%) of 45 primary OSCC tissues. Additionally, 57 OSCC tissue specimens were examined by immunohistochemical staining of protein showing down-regulation of DMBT1 protein in 31 (56.1%) of the 57 primary OSCC tissue specimens. To assess restoration of DMBT1 expression by demethylation of promoter region, the 9 cell lines were treated with 5-aza-2-deoxycytidine (5-Aza-C), one of the DNA demethylating agents. Six (66.7%) of 9 cell lines demonstrated restoration of DMBT1 expression after 5-Aza-C treatment. These results suggest that DMBT1 gene is involved in OSCC oncogenesis and/or progression and that methylation of promoter region is one of the important mechanisms suppressing the DMBT1 gene expression.
Insights
The Deleted in Malignant Brain Tumors 1 (DMBT1) gene is downregulated in oral squamous cell carcinoma (OSCC). Promoter methylation suppresses DMBT1 expression, suggesting its role as a tumor suppressor in OSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The Deleted in Malignant Brain Tumors 1 (DMBT1) gene is a candidate tumor suppressor implicated in various cancers.
- Its specific role and regulation in oral squamous cell carcinoma (OSCC) remain largely uncharacterized.
Purpose of the Study:
- To investigate the involvement of the DMBT1 gene in the oncogenesis and progression of OSCC.
- To determine the expression status and regulatory mechanisms of DMBT1 in OSCC.
Main Methods:
- Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to assess DMBT1 gene expression in OSCC cell lines and tissues.
- Immunohistochemical staining to evaluate DMBT1 protein levels in OSCC specimens.
- Treatment of OSCC cell lines with 5-aza-2-deoxycytidine (5-Aza-C) to assess promoter demethylation effects on DMBT1 expression.
Main Results:
- DMBT1 expression was found to be downregulated or deleted in all 9 examined OSCC cell lines.
- Downregulation of DMBT1 was observed in 40% of primary OSCC tissues at the gene expression level and in 56.1% at the protein level.
- Treatment with the demethylating agent 5-Aza-C restored DMBT1 expression in 66.7% of the OSCC cell lines.
Conclusions:
- The DMBT1 gene plays a role in OSCC oncogenesis and/or progression.
- Promoter methylation is identified as a significant mechanism contributing to the suppression of DMBT1 gene expression in OSCC.
- These findings highlight DMBT1 as a potential therapeutic target in OSCC.
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