Kinoshita Takashi, Nomoto Shuji, Kodera Yasuhiro, Koike Masahiko, Fujiwara Michitaka, Nakao Akimasa
Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hepatogastroenterology. 2011 May-Jun;58(107-108):1051-6.
BACKGROUND/AIMS: Expression of secreted frizzled-related protein (SFRP) genes is silenced by aberrant methylation of the promoter region in several cancers. SFRP genes have recently been mapped on chromosome 8p12-p12.1 (SFRP1), 4q31.3 (SFRP2) and 10q24.1 (SFRP5), respectively. Interestingly, the SFRP family genes are located where the frequent LOH have been shown in gastric cancer samples.
Methylation status and expression of SFRP genes were investigated in gastric cancer cell lines and surgically resected specimens.
A significant decrease in the expression of SFRP1 and SFRP5 was observed in gastric cancer compared with corresponding normal gastric tissues. The SFRP1 gene was hypermethylated in all 35 cancer tissues and corresponding non-cancerous tissues, as well as all seven gastric cancer cell lines, whereas SFRP2 gene was methylated in 83% of cancer tissues and 69% of normal epithelium, and SFRP5 in 43% and 54% of the same groups, respectively. Although gender, age, tumor size, pathological type, depth of tumor and TNM stage were not significantly correlated with the expression of SFRP genes, a significant decrease in the SFRP1 expression score was observed among gastric cancer with lymph node metastasis.
These results indicate the possibility that SFRP1 and 5 genes function as tumor suppressors, the down-regulation of which not only contributes to carcinogenesis but is also associated to some extent with the metastatic potential of cancer cells.
背景/目的：在几种癌症中，分泌型卷曲相关蛋白（SFRP）基因的表达因启动子区域异常甲基化而沉默。最近，SFRP基因分别定位于染色体8p12 - p12.1（SFRP1）、4q31.3（SFRP2）和10q24.1（SFRP5）。有趣的是，SFRP家族基因所在位置在胃癌样本中显示出频繁的杂合性缺失。
研究了胃癌细胞系和手术切除标本中SFRP基因的甲基化状态和表达情况。
与相应的正常胃组织相比，胃癌中SFRP1和SFRP5的表达显著降低。SFRP1基因在所有35个癌组织、相应的非癌组织以及所有7个胃癌细胞系中均发生高甲基化，而SFRP2基因在83%的癌组织和69%的正常上皮组织中发生甲基化，SFRP5在同组中的甲基化率分别为43%和54%。尽管性别、年龄、肿瘤大小、病理类型、肿瘤深度和TNM分期与SFRP基因的表达无显著相关性，但在有淋巴结转移的胃癌中，SFRP1表达评分显著降低。
这些结果表明SFRP1和5基因可能作为肿瘤抑制因子发挥作用，其下调不仅有助于致癌，而且在一定程度上与癌细胞的转移潜能相关。
