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

¹ Department of Cancer Molecular Epidemiology, Shantou University Medical College, Shantou, Guangdong, China
² Tumour Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
³ Biology College, Shandong Normal University, Jinan, Shandong, China

Correspondence to:
Dr Ke Li, Department of Cancer Molecular Epidemiology, Shantou University Medical College, 22 XinLing Road, Shantou 515041, Guangdong, China; kli{at}stu.edu.cn

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.

Abbreviations: MSP, methylation-specific PCR; 5-Aza-CdR, 5-aza-2'-deoxycytidine; OSCC, oesophageal squamous cell carcinoma