Cairo G, Ferrero M, Biondi G, Colombo M P
Istituto Patologia Generale, Centro di Studio sulla Patologia Cellulare del CNR, Milano, Italy.
Br J Cancer. 1992 Jul;66(1):27-31. doi: 10.1038/bjc.1992.211.
A set of growth arrest-specific (gas) genes negatively regulated by serum has been identified. We report the analysis of the expression of one of them (gas-1) in transformed cells. We found a down regulation of gas-1 expression in NIH 3T3 cells transfected in vitro with an activated Ha-ras oncogene. In five chemically-induced mouse tumours grown in vivo the amounts of gas-1 mRNA were largely different but not related to the proliferating activity (evaluated by both H3 histone expression and 3H-thymidine incorporation into DNA). The amount of gas-1 mRNA in the tumours was in general higher than in normal tissues. Expression of c-myc was also evaluated and found to be high in tumours which exhibited low gas-1 expression. Two fibrosarcomas, CA-2 and CB-20, with similar phenotype, similar growth rate, different expression of c-myc and 100-fold difference in gas-1 expression were further investigated and gas-1 expression was found to be correlated with the expression of a differentiated function (as judged from collagen expression). Cell lines derived from CA-2 and CB-20 and maintained under different culture conditions showed that the cell cycle regulation and serum response of gas-1 expression were lost in CA-2. The higher steady state level of gas-1 mRNA in spite of a shorter mRNA half life suggests that in CB-20 cells the gas-1 gene is transcribed faster than in CA-2 cells indicating that transcriptional regulation is the major determinant of gas-1 gene expression in tumour cells. The finding of gas-1 expression in tumour cells suggests that its expression is not sufficient to maintain cells into quiescence, however, as a marker specific for the G0 phase, it could be useful, in conjunction with other growth related genes, to define the cell cycle distribution of a cell population.
一组受血清负调控的生长停滞特异性（gas）基因已被鉴定出来。我们报告了其中一个基因（gas-1）在转化细胞中的表达分析。我们发现，用活化的Ha-ras癌基因体外转染的NIH 3T3细胞中，gas-1表达下调。在体内生长的5种化学诱导的小鼠肿瘤中，gas-1 mRNA的量差异很大，但与增殖活性无关（通过H3组蛋白表达和3H-胸腺嘧啶掺入DNA来评估）。肿瘤中gas-1 mRNA的量通常高于正常组织。还评估了c-myc的表达，发现在gas-1表达低的肿瘤中其表达较高。对具有相似表型、相似生长速率、不同c-myc表达且gas-1表达相差100倍的两种纤维肉瘤CA-2和CB-20进行了进一步研究，发现gas-1表达与一种分化功能的表达相关（根据胶原蛋白表达判断）。从CA-2和CB-20衍生并在不同培养条件下维持的细胞系表明，CA-2中gas-1表达的细胞周期调控和血清反应丧失。尽管mRNA半衰期较短，但gas-1 mRNA的稳态水平较高，这表明在CB-20细胞中gas-1基因的转录速度比在CA-2细胞中快，这表明转录调控是肿瘤细胞中gas-1基因表达的主要决定因素。在肿瘤细胞中发现gas-1表达表明，其表达不足以使细胞维持静止状态，然而，作为G0期特异性标志物，它可能与其他生长相关基因一起，有助于确定细胞群体的细胞周期分布。
