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p300 expression repression by hypermethylation associated with tumour invasion and metastasis in oesophageal squamous cell carcinoma
  1. Changsong Zhang1,
  2. Ke Li1,
  3. Lixin Wei2,
  4. Zhengyou Li3,
  5. Ping Yu1,
  6. Lijuan Teng1,
  7. Kusheng Wu1,
  8. Jin Zhu1
  1. 1
    Department of Cancer Molecular Epidemiology, Shantou University Medical College, Shantou, Guangdong, China
  2. 2
    Tumour Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
  3. 3
    Biology College, Shandong Normal University, Jinan, Shandong, China
  1. Dr Ke Li, Department of Cancer Molecular Epidemiology, Shantou University Medical College, 22 XinLing Road, Shantou 515041, Guangdong, China; kli{at}stu.edu.cn

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.

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Footnotes

  • Competing interests: None declared.

  • Abbreviations:
    MSP
    methylation-specific PCR
    5-Aza-CdR
    5-aza-2′-deoxycytidine
    OSCC
    oesophageal squamous cell carcinoma

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