ADRM1-amplified metastasis gene in gastric cancer
ADRM1-amplified metastasis gene in gastric cancer
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DOI：
10.1002/gcc.22262
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发表时间：
2015-08-01
影响因子：
3.7
通讯作者：
Slamon, Dennis J.
中科院分区：
文献类型：
--
作者：
Fejzo, Marlena S.;Anderson, Lee;Slamon, Dennis J.
蛋白酶体泛素受体 ADRM1 已被证明是上皮癌（包括卵巢癌和结肠癌）中 20q13.3 扩增的驱动因素。我们对 16 个胃癌细胞系进行阵列 CGH，发现 20q13.3 扩增率为 19%，胃癌细胞系 AGS 中的最小扩增区域跨越 1 Mb 区域，包括 ADRM1。表达微阵列分析显示最小区域中仅两个基因 ADRM1 和 OSBPL2 过表达。虽然 ADRM1 和 OSBPL2 的 RNAi 敲低导致生长略有下降，但只有 ADRM1 RNAi 敲低才导致软琼脂的迁移和生长显着减少。用 ADRM1 抑制剂 RA190 处理 AGS 细胞会导致蛋白酶体受到抑制，但 ADRM1 的 RNAi 敲除却不会。然而，ADRM1 的 RNAi 敲低导致包括 MNAT1、HRS 和 EGFR 在内的特定蛋白质显着减少。我们假设 ADRM1 可能在 ADRM1 扩增的胃癌中发挥作用，改变特定癌基因的蛋白质水平，从而导致转移潜力增加。独立于蛋白酶体抑制的 ADRM1 选择性抑制可能会导致 ADRM1 扩增胃癌的靶向治疗。现在有必要使用体内模型来验证这些发现。 (c) 2015 年 Wiley 期刊公司。
The proteasome ubiquitin receptor ADRM1 has been shown to be a driver for 20q13.3 amplification in epithelial cancers including ovarian and colon cancer. We performed array-CGH on 16 gastric cancer cell lines and found 20q13.3 to be amplified in 19% with the minimal amplified region in gastric cancer cell line AGS spanning a 1 Mb region including ADRM1. Expression microarray analysis shows overexpression of only two genes in the minimal region, ADRM1 and OSBPL2. While RNAi knockdown of both ADRM1 and OSBPL2 led to a slight reduction in growth, only ADRM1 RNAi knockdown led to a significant reduction in migration and growth in soft-agar. Treatment of AGS cells with the ADRM1 inhibitor RA190 resulted in proteasome inhibition, but RNAi knockdown of ADRM1 did not. However, RNAi knockdown of ADRM1 led to a significant reduction in specific proteins including MNAT1, HRS, and EGFR. We hypothesize that ADRM1 may act in ADRM1-amplified gastric cancer to alter protein levels of specific oncogenes resulting in an increase in metastatic potential. Selective inhibition of ADRM1 independent of proteasome inhibition may result in a targeted therapy for ADRM1-amplified gastric cancer. In vivo models are now warranted to validate these findings. (c) 2015 Wiley Periodicals, Inc.