Fhit loss in lung preneoplasia: Relation to DNA damage response checkpoint activation
Fhit loss in lung preneoplasia: Relation to DNA damage response checkpoint activation
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DOI：
10.1016/j.canlet.2009.10.017
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发表时间：
2010-05-28
期刊：
影响因子：
9.7
通讯作者：
Vecchione, Andrea
中科院分区：
文献类型：
--
作者：
Cirombella, Roberto;Montrone, Giuseppe;Vecchione, Andrea
FHIT 基因座杂合性的丧失与 DNA 损伤反应检查点蛋白的激活同时发生；因此，脆弱位点的损伤可能会触发检查点激活。我们检查了邻近非小细胞肺癌的癌前病变中 Fhit 和激活检查点蛋白表达的变化。分析表达评分以了解蛋白质与病变类型之间的成对关联和相关性。增生性和不典型增生病灶核γ H2AX表达呈阳性； 12/20 发育异常病变的 Fhit 表达呈阴性。 Fhit 阳性病变显示大多数检查点蛋白的表达，而 Fhit 阴性病变显示 Chk1 和 phosphoChk1 表达缺失。结果表明，Fhit 表达缺失与发育不良中激活的 Chk1 缺失显着直接相关，并表明 Fhit 缺失与检查点活性调节之间存在联系。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Loss of heterozygosity at the FHIT locus is coincident with activation of DNA damage response checkpoint proteins; thus damage at fragile loci may trigger checkpoint activation. We examined preneoplastic lesions adjacent to non-small cell lung carcinomas for alterations to expression of Fhit and activated checkpoint proteins. Expression scores were analyzed for pair-wise associations and correlations among proteins and type of lesion. Hyperplastic and dysplastic lesions were positive for nuclear gamma H2AX expression; 12/20 dysplastic lesions were negative for Fhit expression. Fhit positive lesions showed expression of most checkpoint proteins examined, while Fhit negative lesions showed absence of expression of Chk1 and phosphoChk1. The results show that loss of expression of Fhit is significantly directly correlated with absence of activated Chk1 in dysplasia, and suggest a connection between loss of Fhit and modulation of checkpoint activity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.