On the Carpet

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-i) in transformed cells. We found a down regulation of gas-I 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-I 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-I 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-I 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-I expression were further investigated and gas-I 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-I expression were lost in CA-2. The higher steady state level of gas-I mRNA in spite of a shorter mRNA half life suggests that in CB-20 cells the gas-I gene is transcribed faster than in CA-2 cells indicating that transcriptional regulation is the major determinant of gas-I gene expression in tumour cells. The finding of gas-I expression in tumour cells suggests that its expression is not sufficient to maintain cells into quiescence, however, as a marker specific for the Go phase, it could be useful, in conjunction with other growth related genes, to define the cell cycle distribution of a cell population. Cellular proliferation in eukaryotes is a highly controlled and complex process involving expression of several genes (Baserga, 1985). Cancer can be seen as an unregulated growth of cells which have escaped intra and extra cellular controls; many regulatory steps of cell proliferation have been shown to be defective in cancer cells (Pardee, 1989). One of the pivotal points in cell proliferation is the transition from the quiescent state, called Go, to the GI phase, in which the chain of molecular events leading to cell duplication is initiated (Pardee, 1989). Many studies have been focused on the identification of genes induced by mitogenic factors during the Go to GI transition (see Herschman, 1989 for review). …