Selective loss of resistant alleles at p15INK4B and p16INK4A genes in chemically-induced rat tongue cancers
Selective loss of resistant alleles at p15INK4B and p16INK4A genes in chemically-induced rat tongue cancers
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DOI：
10.1016/j.oraloncology.2005.11.011
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发表时间：
2006-08-01
期刊：
影响因子：
4.8
通讯作者：
Kitano, Motoo
中科院分区：
文献类型：
--
作者：
Ogawa, Kotaro;Tanuma, Jun-ichi;Kitano, Motoo
我们之前报道过，Dark-Agouti (DA) 和 Wistar/Furth (WF) 大鼠对 4-硝基喹啉 1-氧化物 (4NQO) 诱导的舌癌的易感性是由许多数量性状位点决定的。在本文中，我们进一步检查了大鼠 5 号染色体上的一个暗示性水平的数量性状基因座。对用 4NQO 处理的 130 只 (DA x WF) F2 大鼠的 DNA 组进行分析，显示了一个数量性状基因座，其中包含 p15(INK4B) 和 p16(INK4A)。为了研究这些基因在舌癌发展中可能的相关性，我们检查了 100 只 (DA x WF) F1 大鼠中 45 只 4NQO 诱导的舌癌的杂合性。大的晚期舌癌中p15(INK4B)和p16(INK4A)基因杂合性丢失的发生率分别为37.8%和40.0%，并且WF等位基因选择性丢失。晚期肿瘤中抑癌基因启动子区域杂合性和甲基化的积累表明它们可能在舌癌进展中发挥作用。 (c) 2005 Elsevier Ltd. 保留所有权利。
We previously reported that susceptibility to 4-nitroquinotine 1-oxide (4NQO)-induced tongue cancer in Dark-Agouti (DA) and Wistar/Furth (WF) rats was determined by a number of quantitative trait loci. In this article, we further scrutinized one of the quantitative trait loci at a suggestive level on rat chromosome 5. Analyzing a DNA panel of 130 (DA x WF) F2 rats treated with 4NQO showed a quantitative trait loci, containing p15(INK4B) and p16(INK4A). To study the possible relevance of these genes in the development of tongue cancer, we examined 45 4NQO-induced tongue cancers in 100 (DA x WF) F1 rats for toss of heterozygosity. The incidence of toss of heterozygosity at p15(INK4B) and p16(INK4A) genes in large advanced tongue cancers was 37.8% and 40.0%, respectively, and the WF allele was selectively lost. Accumulation of toss of heterozygosity and methylation of the promoter regions in the tumour suppressor genes in advanced tumours suggests that they may play a role in tongue cancer progression. (c) 2005 Elsevier Ltd. All rights reserved.