Alpha-fetoprotein producing gastric cancer lacks transcription factor ATBF1

被引:63
作者
Kataoka, H
Miura, Y
Joh, T
Seno, K
Tada, T
Tamaoki, T
Nakabayashi, H
Kawaguchi, M
Asai, K
Kato, T
Itoh, M
机构
[1] Nagoya City Univ, Sch Med, Dept Bioregulat Res, Mizuhi Ku, Nagoya, Aichi 4678601, Japan
[2] Nagoya City Univ, Sch Med, Dept Internal Med 1, Nagoya, Aichi 4678601, Japan
[3] Nagoya City Univ, Sch Nursing, Dept Pathol, Mizuhi Ku, Nagoya, Aichi 4678601, Japan
[4] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada
[5] Hokkaido Univ, Sch Med, Dept Biochem, Sapporo, Hokkaido 060, Japan
[6] Toyama Med & Pharmaceut Univ, Fac Med, Dept Pathol, Toyama 9300194, Japan
关键词
AFP (Alpha-fetoprotein); AFP-GC (AFP producing gastric cancer); ATBF1 (AT motif binding factor 1); HNF1 (hepatocyte nuclear factor 1);
D O I
10.1038/sj.onc.1204160
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Alpha-fetoprotein (AFP) producing gastric cancer (AFP-GC) is very malignant and highly metastatic compared with common gastric cancer. However, the causal relationship between AFP production and the high malignancy of AFP-GC is unclear. We investigated AFP gene regulation in AFP-GC by an active transcription factor, HNF1 (hapatocyte nuclear factor 1) and a repressive transcription factor, ATBF1 (AT motif binding factor 1), RNase protection assays revealed that the production of AFP in gastric cancer cells did not directly associate with HNF1 expression. An inverse relation between the expressions of ATBF1 and AFP was clearly observed in gastric cancer cells. CAT assays showed the direct inhibition of AFP gene expression by ATBF1, Methylation analysis of the AFP promoter region in gastric cancer cells suggested that methylation itself could not explain the silencing of the AFP gene. Immunohistochemistry of resected clinical samples revealed that AFP producing cells lacked ATBF1 immunoreactivity, Our data suggests that the absence of ATBF1 is responsible for AFP gene expression in gastric cancer, and the absence of ATBF1 is a distinct characteristic of AFP-GC and might be important for its highly malignant nature.
引用
收藏
页码:869 / 873
页数:5
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