Jang Seok Hoon, Park Jun Won, Kim Hyo Rim, Seong Je Kyung, Kim Hark Kyun
Biomolecular Function Research Branch, National Cancer Center, 323 Ilsanro, Ilsandong, Goyang, 410-769, Gyeonggi, Republic of Korea.
Clin Exp Metastasis. 2014 Aug;31(6):727-33. doi: 10.1007/s10585-014-9663-4. Epub 2014 Jun 27.
We searched for candidate target genes in metastatic gastric cancer, using comparative genomic hybridization (CGH) and mRNA expression array analysis of endoscopic biopsy samples collected from 32 patients. Recurrent amplicons included 17q21.2 (36,569,293-37,307,055), 8q24.13-q24.21 (126,357,475-130,159,285), and 20q13.33 (60,211,249-61,382,787). In this paper, we focused on the 1.1-Mb genomic region containing 24 genes in chromosome 20q13.33 (from 60,211,249 to 61,382,787), the third most frequent amplicon that was amplified in three of 32 patients (9.4 %), with log2 tumor/reference ratios ranging from 0.6 to 1.5. Of three genes in the 20q13.33 amplicon, ADRM1 was chosen for functional analyses. ADRM1 knockdown suppressed the proliferation of two human gastric cancer cells, SNU-601 and SNU-216. Overexpression of Adrm1 promoted cell proliferation of conditionally-immortalized, mouse ImSt gastric epithelial cells, with increased S1 phase fraction and decreased expression of p21(Cip1). These results collectively indicate that ADRM1 promoted gastric epithelial cell proliferation by cell cycle progression. Therefore, ADRM1 is a candidate target gene in the chromosome 20q13.33 amplicon that may possibly be linked to development of gastric cancer.
我们利用比较基因组杂交（CGH）和对32例患者内镜活检样本进行的mRNA表达阵列分析，在转移性胃癌中寻找候选靶基因。反复出现的扩增子包括17q21.2（36,569,293 - 37,307,055）、8q24.13 - q24.21（126,357,475 - 130,159,285）和20q13.33（60,211,249 - 61,382,787）。在本文中，我们聚焦于20号染色体q13.33区域（从60,211,249到61,382,787）包含24个基因的1.1 Mb基因组区域，该区域是第三常见的扩增子，在32例患者中有3例（9.4%）出现扩增，log2肿瘤/对照比值在0.6至1.5之间。在20q13.33扩增子中的三个基因中，选择ADRM1进行功能分析。ADRM1基因敲低抑制了两种人胃癌细胞SNU - 601和SNU - 216的增殖。Adrm1的过表达促进了条件永生化小鼠ImSt胃上皮细胞的增殖，增加了S1期比例并降低了p21（Cip1）的表达。这些结果共同表明，ADRM1通过细胞周期进程促进胃上皮细胞增殖。因此，ADRM1是20q13.33扩增子中的一个候选靶基因，可能与胃癌的发生发展有关。
