Schiemann S, Schwirzke M, Brünner N, Weidle U H
Boehringer Mannheim GmbH, Penzberg, Germany.
Clin Exp Metastasis. 1998 Feb;16(2):129-39. doi: 10.1023/a:1021941203905.
As a model system for the identification of genes involved in the progression of human breast cancer, differential gene expression in cell lines MCF-7 and MCF-7ADR was investigated. The latter cell line is derived from the former. Cell line MCF-7 is estrogen receptor-positive, vimentin-negative and uninvasive in the Matrigel outgrowth assay and in the nude mouse, while MCF-7ADR is estrogen receptor-negative, hormone-resistant, vimentin-positive, invasive in the Matrigel outgrowth assay and in the nude mouse and resistant to adriamycin due to overexpression of glycoprotein gp170. We have shown that tumor progression in this model system is mediated by transcriptional regulation of mitochondria-related genes, proteases, transmembrane receptors and cell cycle-related gene proteins. Among the genes differentially regulated at the transcriptional level in the cell lines MCF-7 and MCF-7ADR are a new mitochondrial transcript, mitochondrial creatine kinase, matrix metalloproteinase-1, stromelysin-3, urokinase and its receptor, tissue factor, E-cadherin, epidermal growth factor receptor, transmembrane proteins Mat-8 and progression associated protein (PAP), cyclin E, cyclin-dependent kinase-2 and cell cycle inhibitory proteins p16, p21 and p27.
作为一种用于鉴定参与人类乳腺癌进展的基因的模型系统，研究了MCF-7和MCF-7ADR细胞系中的差异基因表达。后一种细胞系源自前一种细胞系。MCF-7细胞系在基质胶生长试验和裸鼠中是雌激素受体阳性、波形蛋白阴性且无侵袭性，而MCF-7ADR是雌激素受体阴性、激素抵抗性、波形蛋白阳性、在基质胶生长试验和裸鼠中具有侵袭性且由于糖蛋白gp170的过表达而对阿霉素耐药。我们已经表明，在这个模型系统中肿瘤进展是由线粒体相关基因、蛋白酶、跨膜受体和细胞周期相关基因蛋白的转录调控介导的。在MCF-7和MCF-7ADR细胞系中在转录水平上差异调节的基因包括一种新的线粒体转录本、线粒体肌酸激酶、基质金属蛋白酶-1、基质溶解素-3、尿激酶及其受体、组织因子、E-钙黏蛋白、表皮生长因子受体、跨膜蛋白Mat-8和进展相关蛋白（PAP）、细胞周期蛋白E、细胞周期蛋白依赖性激酶-2以及细胞周期抑制蛋白p16、p21和p27。
