Abe M, Kufe D
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):282-6. doi: 10.1073/pnas.90.1.282.
The present studies have examined the sequences responsible for regulating transcription of the human DF3 breast carcinoma-associated antigen (MUC1) gene. A region 1656 base pairs upstream to the DF3 transcription initiation site was fused to the chloramphenicol acetyltransferase gene. Transient expression assays using a series of deleted constructs demonstrated that the region from position -618 contains the regulatory sequences necessary for DF3 transcription in human MCF-7 breast cancer cells. Further analysis with internal deletion vectors and heterologous promoter constructs indicated the involvement of cis-acting elements in the fragment extending from positions -598 to -485. By gel retardation and DNA footprinting, we have identified a protein in MCF-7 cells that recognizes sequences between positions -505 and -485. The results of Southwestern studies demonstrate that this protein has an apparent molecular mass of 45 kDa. Taken together, these results suggest that DF3 gene transcription is regulated by a previously undescribed transacting factor.
目前的研究已经检测了负责调控人类DF3乳腺癌相关抗原(MUC1)基因转录的序列。在DF3转录起始位点上游1656个碱基对的区域与氯霉素乙酰转移酶基因融合。使用一系列缺失构建体的瞬时表达分析表明,从-618位开始的区域包含人MCF-7乳腺癌细胞中DF3转录所需的调控序列。用内部缺失载体和异源启动子构建体进行的进一步分析表明,从-598位延伸至-485位的片段中存在顺式作用元件。通过凝胶阻滞和DNA足迹法,我们在MCF-7细胞中鉴定出一种能识别-505位至-485位之间序列的蛋白质。蛋白质印迹研究结果表明,这种蛋白质的表观分子量为45 kDa。综上所述,这些结果表明DF3基因转录受一种以前未描述的反式作用因子调控。