DCC promoter hypermethylation in esophageal squamous cell carcinoma.
Deleted in Colorectal Cancer (DCC) is a putative tumor suppressor gene, whose loss has been implicated in colorectal tumorigenesis. Decreased or loss of DCC expression has been demonstrated in a number of human cancers, including esophageal cancer. In this study, we analyzed esophageal squamous cell carcinoma (ESCC) cell lines and primary ESCCs as well as normal esophageal tissues for DCC methylation by bisulfite sequencing, methylation-specific PCR (MSP) and/or quantitative methylation-specific PCR (qMSP). When a qMSP cut-off value for positivity was set to 1.0, DCC methylation was detected in 10 of 12 ESCC cell lines tested, 74% of primary ESCCs (n = 70), 0% of corresponding normal esophageal tissues (n = 20) and 0% of normal esophagus from healthy individuals (n = 19). DCC expression was undetectable in the majority of ESCC cell lines, and treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reactivated gene expression. DCC overexpression suppressed colony formation in ESCC cell lines, suggesting that DCC may function as a tumor suppressor gene in the esophagus. However, DCC methylation was not associated with any clinical or pathologic parameters measured. We have demonstrated that DCC methylation is a frequent and cancer-specific event in primary ESCCs, suggesting that DCC and associated pathways may represent a new diagnostical therapeutic target.
Park
Hannah Lui
HL
Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Kim
Myoung Sook
MS
Yamashita
Keishi
K
Westra
William
W
Carvalho
Andre Lopes
AL
Lee
Juna
J
Jiang
Wei-Wen
WW
Baek
Jin Hyen
JH
Liu
Junwei
J
Osada
Motonobu
M
Moon
Chul-So
CS
Califano
Joseph A
JA
Mori
Masaki
M
Sidransky
David
D
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D042241:Early Diagnosis; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D016163:Genes, DCC; D016147:Genes, Tumor Suppressor; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction