Fhit loss in lung preneoplasia: Relation to DNA damage response checkpoint activation
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- 作者：Roberto Cirombella ; Giuseppe Montrone ; Antonella Stoppacciaro ; Simona Giglio ; Stefano Volinia ; Paolo Graziano ; Kay Huebner ; Andrea Vecchione
- 关键词：Fhit ; Preneoplastic lesions of lung ; DNA damage response checkpoint ; Chromosome fragile sites ; Squamous dysplasia
- 刊名：Cancer Letters
- 出版年：2010
- 出版时间：28 May 2010
- 年：2010
- 卷：291
- 期：2
- 页码：230-236
- 全文大小：395 K
文摘
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 γH2AX 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.