Mcs5c: a mammary carcinoma susceptibility locus located in a gene desert that associates with tenascin C expression.
Mcs5c: a mammary carcinoma susceptibility locus located in a gene desert that associates with tenascin C expression.
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Mcs5c：位于基因荒漠中的乳腺癌易感位点，与生腱蛋白 C 表达相关。
DOI：
10.1158/1940-6207.capr-10-0187
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Gould,MichaelN
中科院分区：
文献类型：
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作者：
Veillet,AdelineL;Haag,JillD;Remfert,JaneL;Meilahn,AmandaL;Samuelson,DavidJ;Gould,MichaelN
据估计，遗传因素至少占女性患乳腺癌风险的 30%。我们使用 Wistar Furth (WF) 和 Wistar京都 (WKy) 品系开发了一种大鼠模型，以从基因上鉴定乳腺癌易感性位点。乳腺癌易感位点Mcs5c 的WKy 等位基因先前已被证明可在暴露于7,12-二甲基苯并-[a]蒽(DMBA) 后降低癌症的多重性。本研究利用WF.WKy同系系对Mcs5c进行精细定位。Mcs5c位于大鼠5号染色体上约176 kb的区域。使用两种不同模型诱导乳腺癌发生后，与WF纯合同源对照相比，含有窄Mcs5cWKy间隔的Mcs5c同源系之一显示出平均癌数量减少40%。根据基因图谱，Mcs5 基因座位于基因荒漠中，因此缺乏基因和带注释的 RNA；因此，Mcs5c 中的遗传元件被假设可以调节基因座外基因的表达。 Tenascin c (Tnc) 被确定为候选基因，因为与 WF 纯合同源对照相比，其在 Mcs5cWKy 纯合同源雌性胸腺和卵巢组织中的表达减少。这种等位基因特异性差异表达是环境控制的。癌症预防研究； 4(1)； 97–106。 ©2011 AACR。
Genetic factors have been estimated to account for at least 30% of a woman's risk to develop breast cancer. We have developed a rat model using Wistar Furth (WF) and Wistar Kyoto (WKy) strains to genetically identify mammary cancer susceptibility loci. The WKy allele of the mammary carcinogenesis susceptibility locusMcs5c, was previously shown to reduce carcinoma multiplicity after 7,12-dimethylbenz-[a]anthracene (DMBA) exposure. In this study,Mcs5cwas fine-mapped using WF.WKy congenic lines.Mcs5cwas located to a region of approximately 176 kb on rat chromosome5. One of theMcs5ccongenic lines containing a narrowMcs5cWKy interval displayed a 40% decrease in average carcinoma number compared with WF-homozygous congenic controls after mammary carcinogenesis induction using two different models. As genetically mapped, theMcs5clocus is located in a gene desert and thus is devoid of genes and annotated RNAs; thus, a genetic element inMcs5cwas hypothesized to regulate the expression of genes outside the locus. Tenascin c (Tnc) was identified as a candidate gene due to its reduced expression in thymus and ovarian tissues ofMcs5cWKy-homozygous congenic females compared with WF-homozygous congenic controls. This allele-specific differential expression is environmentally controlled.Cancer Prev Res; 4(1); 97–106. ©2011 AACR.