Bera T K, Tsukamoto T, Panda D K, Huang T, Guzman R C, Hwang S I, Nandi S
Cancer Research Laboratory, University of California at Berkeley 94720, USA.
Biochem Biophys Res Commun. 1998 Jul 30;248(3):835-40. doi: 10.1006/bbrc.1998.9059.
Endogenous retrovirus sequences are present in the genome of a wide variety of animal species. The activation of the proto-oncogenes of the ras family, particularly c-Ha-ras, by either point mutation or overexpression, has been shown to be associated with a vast number, of different cancers. here we report that the insertion of a defective retrovirus in the -1 intron of rat c-Ha-ras is responsible for the activation of the gene by over 10-fold overexpression in an MNU-induced rat mammary cancer. A portion of the 3' end of the retroviral sequence is expressed as a part of the c-Ha-ras transcript in the carcinoma tissue, indicating the direct involvement of this element in the transcription of the c-Ha-ras gene. The c-Ha-ras structural gene transcribed by the promoter of the defective retroviral element can neoplastically transform the NIH 3T3 cell line upon transfection.
内源性逆转录病毒序列存在于多种动物物种的基因组中。已表明，原癌基因ras家族，特别是c-Ha-ras，通过点突变或过表达激活，与大量不同癌症相关。在此我们报告，在大鼠c-Ha-ras的-1内含子中插入缺陷型逆转录病毒，导致该基因在N-甲基-N-亚硝基脲（MNU）诱导的大鼠乳腺癌中过表达超过10倍而被激活。逆转录病毒序列3'端的一部分在癌组织中作为c-Ha-ras转录本的一部分表达，表明该元件直接参与c-Ha-ras基因的转录。由缺陷型逆转录病毒元件的启动子转录的c-Ha-ras结构基因在转染后可使NIH 3T3细胞系发生肿瘤转化。
