Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration.
Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration.
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DOI：
10.18632/oncotarget.2097
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Copland JA
中科院分区：
文献类型：
--
作者：
Von Roemeling CA;Marlow LA;Radisky DC;Rohl A;Larsen HE;Wei J;Sasinowska H;Zhu H;Drake R;Sasinowski M;Tun HW;Copland JA
目前，在晚期肾透明细胞癌(CcRCC)患者中，缺乏导致疾病长期减弱或消退的靶向治疗。我们小组实施了高通量基因分析和高通量增殖筛查，以在功能水平上调查大量过度表达基因的遗传贡献，以努力更好地了解参与肿瘤发生和发展的因素。患者基因阵列分析发现，与匹配的正常肾组织相比，患者ccRCC的转录本持续升高。随后进行了高通量慢病毒筛选，在四个ccRCC细胞系中独立定位于基因阵列中发现的195个过表达的转录本。这揭示了31个促进ccRCC细胞增殖的“Hit”。许多已确定的命中结果不仅首次出现在ccRCC的背景下，而且有几个以前没有与癌症有关。我们进一步描述了一组HITS在肿瘤细胞侵袭中的作用。综上所述，这些发现揭示了可能在ccRCC致瘤性中起关键作用的途径，并确定了新的候选因素，可以作为晚期ccRCC患者治疗干预或诊断/预后生物标志物的靶点。
Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression. Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 ‘hits’ that contribute to ccRCC cell proliferation. Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC.
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影响因子：
5.7
作者：
Cooper SJ;von Roemeling CA;Kang KH;Marlow LA;Grebe SK;Menefee ME;Tun HW;Colon-Otero G;Perez EA;Copland JA
通讯作者：
Copland JA
影响因子：
11.2
作者：
Kort, Eric J.;Farber, Leslie;Teh, Bin T.
通讯作者：
Teh, Bin T.
DOI：
10.1073/pnas.012425299
发表时间：
2002-01-08
影响因子：
11.1
作者：
Ino, Y;Gotoh, M;Hirohashi, S
通讯作者：
Hirohashi, S
影响因子：
8.8
作者：
Baldewijns, M M;Thijssen, V L;Van den Eynden, G G;Van Laere, S J;Bluekens, A M;Roskams, T;van Poppel, H;De Bruine, A P;Griffioen, A W;Vermeulen, P B
通讯作者：
Vermeulen, P B
影响因子：
4.3
作者：
Haddad, Housam;Rini, Brian I.
通讯作者：
Rini, Brian I.