Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations.
Radiation-induced G1 arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations.
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DOI：
10.1038/sj.bjc.6690265
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发表时间：
1999-04
影响因子：
8.8
通讯作者：
Varley, JM
中科院分区：
文献类型：
--
作者：
Boyle, JM;Greaves, MJ;Camplejohn, RS;Birch, JM;Roberts, SA;Varley, JM
在四类早期传代皮肤成纤维细胞中研究了辐射诱导的G1停滞，所述成纤维细胞包括12个正常人、12个杂合（mut/wt）TP 53突变携带者、两个纯合（mut/-）TP 53突变携带者和来自9个Li-Fraumeni综合征或Li-Fraumeni样家族的16个菌株，尽管对所有外显子、外显子-内含子边界、3′和5′非翻译区和启动子区。在酵母中p53等位基因表达的测定中，来自这些非突变菌株的cDNA表现为野生型p53。使用两种不同的检测方法，我们发现G1期阻滞在具有错义突变和一个截短突变的杂合菌株中减少，与正常细胞建立的范围相比。在剪接位点突变的杂合菌株表现得像正常细胞，而纯合（突变/-）菌株表现出极低，或没有，逮捕。来自所有9个非突变家族的菌株的反应均在正常范围内。与先前报道的G1期阻滞和克隆形成的辐射抗性之间的负相关性不同，观察到这些表型不是严格相互依赖的。© 1999癌症研究运动
Radiation-induced G1 arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/–) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon–intron boundaries, 3′ and 5′ untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G1 arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/–) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G1 arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent. © 1999 Cancer Research Campaign
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影响因子：
8.8
作者：
Boyle, J M;Mitchell, E L;Greaves, M J;Roberts, S A;Tricker, K;Burt, E;Varley, J M;Birch, J M;Scott, D
通讯作者：
Scott, D
影响因子：
39.2
作者：
LI, FP;FRAUMENI, JF
通讯作者：
FRAUMENI, JF
影响因子：
3.4
作者：
LITTLE, JB;NAGASAWA, H
通讯作者：
NAGASAWA, H
影响因子：
8
作者：
Schmale, H;Bamberger, C
通讯作者：
Bamberger, C
影响因子：
8
作者：
Lomax, ME;Barnes, DM;Camplejohn, RS
通讯作者：
Camplejohn, RS