Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Genes Chromosomes Cancer. 2011 Jun;50(6):434-41. doi: 10.1002/gcc.20868. Epub 2011 Mar 22.
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.
美国每年大约诊断出 25000 例卵巢癌，其中 75%的病例在晚期，基本上无法治愈。因此，迫切需要改进早期检测工具并开发新的治疗方法。最近，我们发现，在卵巢癌的 20q13 扩增基因中，ADRM1 的过表达与扩增最相关，并且与分期、复发和转移呈显著正相关。此外，ADRM1 的过表达与复发时间和总生存期显著缩短相关。在此，卵巢癌细胞系的阵列-CGH 和微阵列表达提供的证据与原发性肿瘤数据一致，表明 ADRM1 是 20q13 扩增的靶标。在扩增的卵巢细胞系 OAW42 中敲低 ADRM1 导致生长因子 GIPC1 的下调和肿瘤抑制因子 RECK RNA 和蛋白质的上调。在我们的 141 例卵巢原发性肿瘤数据集，ADRM1 的过表达与 GIPC1 的过表达显著相关。此外，ADRM1 的过表达与 RECK 表达之间存在显著的负相关。需要进一步研究以确定靶向敲低 20q13 扩增卵巢癌中的 ADRM1 是否通过下游靶标 GIPC1 和 RECK 导致生长抑制和肿瘤抑制。
