Jansen E, Steenbergh P H, van Schaik F M, Sussenbach J S
Laboratory for Physiological Chemistry, State University of Utrecht, The Netherlands.
Biochem Biophys Res Commun. 1992 Sep 30;187(3):1219-26. doi: 10.1016/0006-291x(92)90433-l.
The human insulin-like growth factor-I (IGF-I) gene contains two alternative leader exons: exons 1 and 2. We have identified, by transient transfection experiments, the putative promoters P1 and P2 upstream of these leader exons. The promoter regions were cloned in front of the luciferase reporter gene and their promoter activities were measured in transfected SK-N-MC (human neuroepithelioma) and OVCAR-3 (human ovarian carcinoma) cells. Both of these cell lines express the IGF-I gene endogenously, resulting in normally sized IGF-I mRNAs of 7.6, 1.3 and 1.1 kb. In SK-N-MC cells, in which P1 is the most active IGF-I promoter, P2 displayed a three times lower promoter activity than P1. However, in OVCAR-3 cells, P2 is four times more active than P1, resulting in an overall 12-fold difference in the relative promoter activities of the two IGF-I gene promoters in these two cell types. This indicates that the IGF-I promoters show a cell type-specific expression pattern.
人类胰岛素样生长因子-I(IGF-I)基因包含两个可变的前导外显子:外显子1和外显子2。我们通过瞬时转染实验,在这些前导外显子上游鉴定出了推定的启动子P1和P2。将启动子区域克隆到荧光素酶报告基因的前面,并在转染的SK-N-MC(人类神经上皮瘤)和OVCAR-3(人类卵巢癌)细胞中测量它们的启动子活性。这两种细胞系均内源性表达IGF-I基因,产生正常大小的7.6、1.3和1.1 kb的IGF-I mRNA。在P1是最活跃的IGF-I启动子的SK-N-MC细胞中,P2的启动子活性比P1低三倍。然而,在OVCAR-3细胞中,P2的活性比P1高四倍,导致这两种细胞类型中两个IGF-I基因启动子的相对启动子活性总体相差12倍。这表明IGF-I启动子表现出细胞类型特异性的表达模式。