Expression of a growth arrest specific gene (gas-1) in transformed cells

Abstract

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.