Knockdown of Ovarian Cancer Amplification Target ADRM1 Leads to Downregulation of GIPC1 and Upregulation of RECK
Knockdown of Ovarian Cancer Amplification Target ADRM1 Leads to Downregulation of GIPC1 and Upregulation of RECK
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DOI：
10.1002/gcc.20868
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发表时间：
2011-06-01
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.;Ginther, Chuck;Slamon, Dennis J.
在美国，每年大约有25，000例卵巢癌被诊断出来，其中75%的病例处于晚期，基本上无法治愈。迫切需要改进的早期检测工具和开发新的治疗方法。最近，我们发现在卵巢癌20q13扩增基因中，ADRM 1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。此外，ADRM 1过表达与较短的复发时间和总生存期显著相关。在此，卵巢癌细胞系的阵列CGH和微阵列表达提供了与ADRM 1是20q13扩增靶的原发肿瘤数据一致的证据。在扩增的卵巢细胞系OAW42中ADRM 1的敲低导致生长因子GIPC 1的下调和肿瘤抑制因子RECK RNA和蛋白的上调。在我们的141例卵巢原发性肿瘤数据集中，ADRM 1过表达与GIPC 1过表达显著相关。此外，ADRM 1的过表达与RECK的表达之间存在显著的负相关。进一步的研究是必要的，以确定是否在20q13扩增的卵巢癌中靶向敲除ADRM 1通过下游靶点GIPC 1和RECK导致生长抑制和肿瘤抑制。(C)2011 Wiley-Liss，Inc.
Approximately 25,000 ovarian cancers are diagnosed in the United States annually, and 75% of cases are in the advanced stage when they are largely incurable. There is a critical need for improved early detection tools and development of novel treatments. 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. In addition, overexpression of ADRM1 correlated significantly with shorter time to recurrence and overall survival. Herein, array-CGH and microarray expression of ovarian cancer cell lines provides evidence consistent with the primary tumor data that ADRM1 is a 20q13 amplification target. Knockdown of ADRM1 in amplified ovarian cell-line OAW42 results in downregulation of growth factor GIPC1 and upregulation of tumor-suppressor RECK RNA and protein. In our dataset of 141 ovarian primary tumors, ADRM1 overexpression significantly correlates with GIPC1 overexpression. In addition, there is a significant anticorrelation between ADRM1 overexpression and RECK expression. Further research is necessary to determine whether targeting knockdown of ADRM1 in 20q13-amplified ovarian cancers results in growth inhibition and tumor suppression via downstream targets GIPC1 and RECK. (C) 2011 Wiley-Liss, Inc.