Rationales for expression and altered expression of apoptotic protease activating factor-1 gene in gastric cancer

• Published in: World journal of gastroenterology : WJG 2007-10, Vol.13 (38), p.5060-5064
• Main Authors: Wang, He-Ling, Bai, Han, Li, Yan, Sun, Jun, Wang, Xue-Qing
• Format: Article
• Language: English
• Subjects: Aged; Apoptotic Protease-Activating Factor 1 - genetics; Apoptotic Protease-Activating Factor 1 - metabolism; Case-Control Studies; DNA Methylation; DNA, Neoplasm - genetics; DNA, Neoplasm - metabolism; Female; Gastric Cancer; Gene Expression Regulation, Neoplastic; Humans; Loss of Heterozygosity - genetics; Male; Middle Aged; Promoter Regions, Genetic - genetics; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v13.i38.5060

To elucidate the relationship between apoptotic protease activating factor-1 (Apaf-1) gene and gastric cancer. Thirty-five postoperative cancer and adjacent normal tissue samples were collected in the present study. Expression of the Apaf-1 gene in these samples was analyzed by semi-quantitative RT-PCR. Loss of heterozygosity (LOH) was used to determine whether there was loss of Apaf-1 gene in domain of 12q22-23 in the samples. Promoter methylation of Apaf-1 gene in the samples was analyzed by methylation specific (MSP) PCR. The expression of Apaf-1 mRNA in gastric cancer tissue samples was 51%. The LOH frequency of D12S346, D12S1706, D12S327, D12S1657 and D12S393 was 33%, 8%, 58%, 12% and 42%, respectively. Fifty percent LOH was found at two sites and 17% LOH at three sites. Apaf-1 mRNA expression decreased significantly in 13 cases (rs=0.487, P=0.003). The rate of Apaf-1 promoter methylation was 49% in gastric cancer tissue samples and 23% in para-cancerous tissue samples. Promoter methylation occurred significantly in 16 of 18 gastric cancer tissue samples with decreased expression of Apaf-1 mRNA rs=0.886, P=10(-6)). The expression of Apaf-1 gene is low in gastric cancer tissues. Methylation of Apaf-1 gene promoter and LOH in domain of 12q22-23 are the main reasons for the expression and altered expression of Apaf-1 gene.