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. Aims: 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 nonneoplastic 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.