Amplification Target ADRM1: Role as an Oncogene and Therapeutic Target for Ovarian Cancer.
Amplification Target ADRM1: Role as an Oncogene and Therapeutic Target for Ovarian Cancer.
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DOI：
10.3390/ijms14023094
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发表时间：
2013-02-01
影响因子：
5.6
通讯作者：
Slamon DJ
中科院分区：
文献类型：
--
作者：
Fejzo MS;Anderson L;von Euw EM;Kalous O;Avliyakulov NK;Haykinson MJ;Konecny GE;Finn RS;Slamon DJ
在美国，每年大约有2.5万例卵巢癌被诊断出来，其中75%处于晚期，基本上无法治愈。迫切需要早期检测工具和新的治疗方法。蛋白酶体泛素受体ADRM1是一种由ADRM1基因编码的蛋白。最近，我们发现在卵巢癌的20q13扩增基因中，ADRM1过表达与扩增高度相关，并且在分期、复发和转移方面显著上调。其过表达与较短的复发时间和总生存率显著相关。阵列- cgh和微阵列表达卵巢癌细胞系提供了与原发肿瘤数据一致的证据，表明ADRM1是20q13扩增靶点。在此，我们在第二个卵巢癌队列中确认了ADRM1扩增子，并定义了一个包含7个基因的262 KB的最小扩增区域。此外，通过在自然扩增的OAW42细胞系中RNAi敲除ADRM1，并在ES2中转染ADRM1过表达，我们发现(1)ADRM1过表达增加了软琼脂中的增殖、迁移和生长，(2)敲除ADRM1导致细胞凋亡。ADRM1敲除的细胞的蛋白质组学分析显示包括cdk活化激酶组装因子MAT1在内的蛋白质失调。综上所述，这些结果表明，扩增的ADRM1参与卵巢癌细胞的增殖、迁移和存活，支持其作为癌基因和卵巢癌新的治疗靶点的作用。
Approximately 25,000 ovarian cancers are diagnosed in the U.S. annually, and 75% are in the advanced stage and largely incurable. There is critical need for early detection tools and novel treatments. Proteasomal ubiquitin receptor ADRM1 is a protein that is encoded by the ADRM1 gene. Recently, we showed that among 20q13-amplified genes in ovarian cancer, ADRM1 overexpression was the most highly correlated with amplification and was significantly upregulated with respect to stage, recurrence, and metastasis. Its overexpression correlated significantly with shorter time to recurrence and overall survival. Array-CGH and microarray expression of ovarian cancer cell lines provided evidence consistent with primary tumor data that ADRM1 is a 20q13 amplification target. Herein, we confirm the ADRM1 amplicon in a second ovarian cancer cohort and define a minimally amplified region of 262 KB encompassing seven genes. Additionally, using RNAi knock-down of ADRM1 in naturally amplified cell line OAW42 and overexpression of ADRM1 via transfection in ES2, we show that (1) ADRM1 overexpression increases proliferation, migration, and growth in soft agar, and (2) knock-down of ADRM1 results in apoptosis. Proteomic analysis of cells with ADRM1 knock-down reveals dysregulation of proteins including CDK-activating kinase assembly factor MAT1. Taken together, the results indicate that amplified ADRM1 is involved in cell proliferation, migration and survival in ovarian cancer cells, supporting a role as an oncogene and novel therapeutic target for ovarian cancer.
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影响因子：
3.7
作者：
Fejzo, Marlena S.;Dering, Judy;Slamon, Dennis J.
通讯作者：
Slamon, Dennis J.
影响因子：
3.7
作者：
Fejzo, Marlena S.;Ginther, Chuck;Slamon, Dennis J.
通讯作者：
Slamon, Dennis J.
DOI：
10.3760/cma.j.issn.0253-3766.2009.01.004
发表时间：
2009-01-01
期刊：
Zhonghua Zhongliu Zazhi
影响因子：
--
作者：
Chen Jie;Dong Xin-shu;Guo Xing-gang
通讯作者：
Guo Xing-gang
影响因子：
37.3
作者：
Jiao Y;Ou W;Meng F;Zhou H;Wang A
通讯作者：
Wang A
影响因子：
4
作者：
Simins, AB;Weighardt, H;Holzmann, B
通讯作者：
Holzmann, B