Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis.
Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis.
复制标题
DOI：
10.1371/journal.pone.0057724
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Toyokuni S
中科院分区：
文献类型：
--
作者：
Yamashita Y;Akatsuka S;Shinjo K;Yatabe Y;Kobayashi H;Seko H;Kajiyama H;Kikkawa F;Takahashi T;Toyokuni S
卵巢透明细胞腺癌（OCC）是一种化疗耐药肿瘤，预后相对较差，常与子宫内膜异位症有关。虽然人们认为氧化应激在这种肿瘤的恶性转化中起一定作用，但导致癌变的特征性分子事件仍不清楚。在这项研究中，基于阵列的比较基因组杂交（CGH）分析显示，在4/13的OCC原发性肿瘤和2/8的OCC细胞系中Met基因扩增。通过基于阵列的CGH分析，在5/21个样品中也观察到AKT 2基因的扩增，AKT 2基因是Met/PI 3 K信号通路的下游组分。在一名患者中，Met和AKT 2基因均扩增。这些发现证实了荧光原位杂交，实时定量PCR，免疫印迹和免疫组织化学。总共使用实时定量PCR评估了73例OCC病例; 37.0%的病例显示Met基因扩增（>4个拷贝），8.2%的病例显示AKT 2扩增。此外，有Met基因扩增的1期和2期患者的生存率显著低于无Met基因扩增的患者（p<0.05）。通过shRNA敲低Met导致具有Met扩增的OCC细胞的存活率降低，这是由于增加的凋亡和细胞衰老，表明Met信号通路在OCC致癌中起重要作用。因此，我们认为，Met通路的靶向抑制可能是OCC的有希望的治疗方法。
Clear cell adenocarcinoma of the ovary (OCC) is a chemo-resistant tumor with a relatively poor prognosis and is frequently associated with endometriosis. Although it is assumed that oxidative stress plays some role in the malignant transformation of this tumor, the characteristic molecular events leading to carcinogenesis remain unknown. In this study, an array-based comparative genomic hybridization (CGH) analysis revealed Met gene amplification in 4/13 OCC primary tumors and 2/8 OCC cell lines. Amplification of the AKT2 gene, which is a downstream component of the Met/PI3K signaling pathway, was also observed in 5/21 samples by array-based CGH analysis. In one patient, both the Met and AKT2 genes were amplified. These findings were confirmed using fluorescence in situ hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemistry. In total, 73 OCC cases were evaluated using real-time quantitative PCR; 37.0% demonstrated Met gene amplification (>4 copies), and 8.2% had AKT2 amplification. Furthermore, stage 1 and 2 patients with Met gene amplification had significantly worse survival than patients without Met gene amplification (p<0.05). Met knockdown by shRNA resulted in reduced viability of OCC cells with Met amplification due to increased apoptosis and cellular senescence, suggesting that the Met signaling pathway plays an important role in OCC carcinogenesis. Thus, we believe that targeted inhibition of the Met pathway may be a promising treatment for OCC.
登录
查看更多内容
影响因子：
64.8
作者：
GIORDANO, S;PONZETTO, C;COMOGLIO, PM
通讯作者：
COMOGLIO, PM
影响因子：
15.9
作者：
Kaposi-Novak, Pal;Lee, Ju-Seog;Thorgeirsson, Snorri S.
通讯作者：
Thorgeirsson, Snorri S.
DOI：
10.4161/cc.8.16.9335
发表时间：
2009-08-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gonzalez E;McGraw TE
通讯作者：
McGraw TE
影响因子：
8.8
作者：
Dent, J;Hall, GD;Bell, S
通讯作者：
Bell, S
DOI：
10.1111/j.1525-1438.2007.01135.x
发表时间：
2008-09-01
影响因子：
4.8
作者：
Koon, E. C.;Ma, P. C.;Mok, S. C.
通讯作者：
Mok, S. C.