Rationales for expression and altered expression of apoptotic protease activating factor-1 gene in gastric cancer.
OBJECTIVE
To elucidate the relationship between apoptotic protease activating factor-1 (Apaf-1) gene and gastric cancer.


METHODS
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.


RESULTS
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)).


CONCLUSIONS
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.
Wang
He-Ling
HL
Department of Gastroenterology, Shengjing Hospital Affiliated to China Medical University, Shenyang110004, Liaoning Province, China.
Bai
Han
H
Li
Yan
Y
Sun
Jun
J
Wang
Xue-Qing
XQ
D000368:Aged; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D004273:DNA, Neoplasm