p300 expression repression by hypermethylation associated with tumour invasion and metastasis in oesophageal squamous cell carcinoma

Abstract

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 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.