E-cadherin expression is commonly downregulated by CpG island hypermethylation in esophageal carcinoma cells.
E-cadherin, a cell adhesion molecule, is regarded as an invasion-suppressor molecule and a prognostic marker in many types of human cancers. Downregulation of E-cadherin is common in esophageal carcinoma and is associated with an increase in invasive and metastatic potential. To study the mechanisms responsible for inactivation of this gene in esophageal squamous cell carcinoma (ESCC), we investigated the methylation status around the 5' promoter region of E-cadherin gene of six ESCC cell lines by methylation-specific polymerase chain reaction, and compared it with E-cadherin protein and mRNA expression. We also studied the methylation status of 20 ESCC clinical specimens. Methylation was noted in four of the six cell lines (one fully methylated and three partially methylated). The completely methylated cell line lacked E-cadherin protein expression and mRNA transcription. E-cadherin expression and transcription were reduced in a partially methylated cell line but preserved in the other partially methylated cell lines. Treatment of E-cadherin-negative carcinoma cells with the demethylating agent, 5-aza-2'-deoxycytidine, induced re-expression of the gene. A high frequency of methylation (16/20, 80%) was also noted in the 20 ESCC clinical samples. Our results indicate that 5' CpG island methylation is common in esophageal carcinoma and may play an important role in downregulation of E-cadherin.
Si
H X
HX
Department of Anatomy, The University of HongKong, Li Shu Fan Building, 5 Sassoon Road, Hong Kong SAR, PR China.
Tsao
S W
SW
Lam
K Y
KY
Srivastava
G
G
Liu
Y
Y
Wong
Y C
YC
Shen
Z Y
ZY
Cheung
A L
AL
D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015820:Cadherins; D004791:Enzyme Inhibitors; D012334:RNA, Neoplasm; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine