Screening for genetic abnormalities involved in ovarian carcinogenesis using retroviral expression libraries
Screening for genetic abnormalities involved in ovarian carcinogenesis using retroviral expression libraries
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DOI：
10.3892/ijo_00000410
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发表时间：
2009-11-01
影响因子：
5.2
通讯作者：
Suzuki, Mitsuaki
中科院分区：
文献类型：
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作者：
Wada, Tomoaki;Yamashita, Yoshihiro;Suzuki, Mitsuaki
本研究的目的是筛选卵巢癌发生相关的基因，以期开发有效的卵巢癌分子靶向治疗方法。我们构建了人卵巢癌细胞系SHIN-3和TYK-CPr的逆转录病毒表达文库，并用3 T3细胞进行了焦点形成试验。结果，从SHIN-3中鉴定出蛋白酶体亚基β 2（PSMB 2）、泛素特异性蛋白酶14（USP 14）和角蛋白8（KRT 8），从TYK-CPr中鉴定出聚合酶H RNA亚基（POLR 2 E）、含T复合体多肽1亚基4（CCT 4）的伴侣蛋白、神经胶质成熟因子β（GMFB）和神经母细胞瘤ras病毒癌基因同源物（NRAS）。NRAS基因分析揭示了在密码子61处的CAA -> AAA取代，导致在位置61处的Glu -> Lys改变。当将突变NRAS引入成纤维细胞中进行表达时，产生了许多转化灶，证实了突变NRAS的转化能力。
The purpose of this study was to screen for genes involved in ovarian carcinogenesis in an attempt to develop an effective molecular-targeted therapy for ovarian cancer. We constructed retroviral expression libraries for the human ovarian cancer cell lines SHIN-3 and TYK-CPr, and performed a focus formation assay with 3T3 cells. As a result, proteasome subunit beta-type 2 (PSMB2), ubiquitin-specific protease 14 (USP14), and keratin 8 (KRT8) were identified from SHIN-3, and polymerase H RNA subunit (POLR2E), chaperonin containing T-complex polypeptide 1 subunit 4 (CCT4), glia maturation factor beta (GMFB), and neuroblastoma ras viral oncogene homolog (NRAS) from TYK-CPr. NRAS gene analysis revealed a CAA -> AAA substitution at codon 61, resulting in a Glu -> Lys change at position 61. When the mutant NRAS was introduced into fibroblasts for its expression, many transformed foci were generated, confirming the transforming ability of the mutant NRAS.