p300 expression repression by hypermethylation associated with tumour invasion and metastasis in oesophageal squamous cell carcinoma.
BACKGROUND
Aberrant promoter methylation is an important mechanism for gene silencing.


OBJECTIVE
To evaluate the promoter methylation status of p300 gene in patients with oesophageal squamous cell carcinoma (OSCC).


METHODS
The methylation status of p300 promoter was analysed by methylation-specific PCR (MSP) in 50 OSCC tissues and the matching non-cancerous tissues. Oesophageal cancer cell lines (ECa-109 and TE-10) were treated with the demethylation agent 5-aza-2'-deoxycytidine (5-Aza-CdR), and p300 mRNA expression was detected by RT-PCR.


RESULTS
p300 methylation was found in 42% (21/50) of the OSCC tissues, but in only 20% (10/50) of the corresponding non-cancerous tissues (p = 0.017). In OSCC samples, 65% of those with deep tumour invasion (adventitia) and 63% samples with metastasis revealed p300 promoter methylation (p<0.05). p300 mRNA expression was observed in 19.0% (4/21) of methylated tumours and 58.6% (17/29) of unmethylated tumours (p = 0.005). In addition, p300 mRNA expression was observed in 40% (4/10) of methylated non-neoplastic tissues and 87.5% (35/40) of unmethylated non-tumours (p = 0.001). The demethylation caused by 5-Aza-CdR increased the p300 mRNA expression levels in oesophageal cancer cell lines.


CONCLUSIONS
p300 transcription silenced by promoter hypermethylation could play a role in the pathogenesis of oesophageal squamous cell carcinoma.
Zhang
Changsong
C
Department of Cancer Molecular Epidemiology, Shantou University Medical College, Shantou, Guangdong, China.
Li
Ke
K
Wei
Lixin
L
Li
Zhengyou
Z
Yu
Ping
P
Teng
Lijuan
L
Wu
Kusheng
K
Zhu
Jin
J
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D000077209:Decitabine; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000077209:Decitabine; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D001374:Azacitidine