Down-regulation of DMBT1 gene expression in human oral squamous cell carcinoma.
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.
Imai
Massao Alberto
MA
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Moriya
Tetsuhiro
T
Imai
Fabiana Lica
FL
Shiiba
Masashi
M
Bukawa
Hiroki
H
Yokoe
Hidetaka
H
Uzawa
Katsuhiro
K
Tanzawa
Hideki
H
D000373:Agglutinins / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins
D000373:Agglutinins; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins