Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer

It has recently been reported that CDH13 expression is silenced by aberrant methylation of the promoter region in several cancers. We examined the methylation status of the CDH13 gene in pancreatic cancer using methylation‐specific PCR (MSP), and detected aberrant methylation of CDH13 in all 6 pancr...

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Bibliographic Details
Published in:Cancer science 2004-07, Vol.95 (7), p.588-591
Main Authors: Sakai, Mitsuru, Hibi, Kenji, Koshikawa, Katsumi, Inoue, Soichiro, Takeda, Shin, Kaneko, Tetsuya, Nakao, Akimasa
Format: Article
Language:English
Subjects:
Aged
Biological and medical sciences
Cadherins - genetics
Cadherins - metabolism
Carcinogens
DNA Methylation
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gene Silencing
Genes, Tumor Suppressor
Humans
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Middle Aged
Neoplasm Staging
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - pathology
Promoter Regions, Genetic
Reverse Transcriptase Polymerase Chain Reaction
Reverse transcription
Tumor cell lines
Tumor Cells, Cultured
Tumors
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Summary:It has recently been reported that CDH13 expression is silenced by aberrant methylation of the promoter region in several cancers. We examined the methylation status of the CDH13 gene in pancreatic cancer using methylation‐specific PCR (MSP), and detected aberrant methylation of CDH13 in all 6 pancreatic cancer cell lines examined. To confirm the status of the CDH13 gene in relation to the methylation pattern, we next examined CDH13 expression in these cell lines using reverse transcription (RT)‐PCR. As expected, no CDH13 expression was detected in any of the 6 pancreatic cancer cell lines. Moreover, 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) treatment of CDH13‐methylated cell lines led to restoration of CDH13 expression. Among primary pancreatic cancers, 19 of 33 (58%) cases exhibited CDH13 methylation, while no cases exhibited it in corresponding normal pancreatic tissues. CDH13 methylation was detected even in relatively early pancreatic cancers, such as stage II cancers and cancers less than 2 cm in diameter. Our results suggest that the aberrant methylation of CDH13 occurs frequently in pancreatic cancer, even at a relatively early stage.
ISSN:1347-9032
1349-7006
DOI:10.1111/j.1349-7006.2004.tb02491.x