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.

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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