Matzinger S A, Chen B, Wang Y, Crist K A, Stoner G D, Kelloff G J, Lubet R A, You M
Department of Pathology, Medical College of Ohio, Toledo 43699, USA.
Gene. 1997 Apr 1;188(2):261-9. doi: 10.1016/s0378-1119(96)00821-9.
Tissue-specific expression of parental K-ras allele(s) was investigated by single-strand conformation polymorphism analysis of the 3' untranslated region of the K-ras gene in normal lung, spleen, liver and kidney from (A/J x TSG-p53) F1 mice. The expression of A/J K-ras allele was equal to that of C57BL/6J allele in normal spleen, liver and kidney. However, transcripts from A/J K-ras allele were found to be 2-12-times greater than those from C57BL/6J allele in lung tissues harvested over a 20-week period. Similar to our previous observation with dimethylnitrosamine- and benzo[a] pyrene-induced lung tumors, K-ras mRNA transcribed from A/J allele was 10-40-times more abundant than those from C57BL/6J allele in all of 40 (A/J x TSG-p53) F1 mouse lung tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. In addition, K-ras mutations (G to A transitions at the second base of codon 12) were detected in 38 of 40 (95%) lung tumors and all of the mutations were found on the allele inherited from the A/J parent. These data demonstrate tissue-specific allele-specific transcription of the K-ras gene and provide further support to the thesis that K-ras allele itself is a primary mouse lung tumor susceptibility gene.
通过对(A/J×TSG-p53)F1小鼠的正常肺、脾、肝和肾中K-ras基因3'非翻译区进行单链构象多态性分析，研究了亲本K-ras等位基因的组织特异性表达。在正常脾、肝和肾中，A/J K-ras等位基因的表达与C57BL/6J等位基因的表达相当。然而，在20周内收集的肺组织中，发现A/J K-ras等位基因的转录本比C57BL/6J等位基因的转录本多2至12倍。与我们之前对二甲基亚硝胺和苯并[a]芘诱导的肺肿瘤的观察结果相似，在由4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁酮诱导的40个(A/J×TSG-p53)F1小鼠肺肿瘤中，所有肿瘤中从A/J等位基因转录的K-ras mRNA比从C57BL/6J等位基因转录的K-ras mRNA丰富10至40倍。此外，在40个肺肿瘤中的38个(95%)中检测到K-ras突变(密码子12第二位的G到A转换)，并且所有突变都出现在从A/J亲本遗传的等位基因上。这些数据证明了K-ras基因的组织特异性等位基因特异性转录，并为K-ras等位基因本身是原发性小鼠肺肿瘤易感基因这一论点提供了进一步的支持。
