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

Abstract

Summary 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.

Expression of a growth arrest specific gene (gas‐6) during liver regeneration: Molecular mechanisms and signalling pathways

“…A number of elements of the positive circuit have been characterized (Almendral et al, 1988;Herschman, 19911, but the more recent identification of several negative effectors (Schneider et al, 1991) underscores the importance of the negative control of cell growth. However, the expression of gas genes in proliferating systems in vivo has received little attention (Bissonnette et al, 1990;Cairo et al, 1992;Spreyer et af., 1991, Welcher et al, 1991. Liver regeneration provides a good experimental system for studying in vivo the events that occur during cell proliferation.…”

“…Total liver RNA extracted according to Chomczynski and Sacchi (1987) was run in 40 pg aliquots in denaturing agarose gels, blotted, fixed, and hybridized to 32Plabelled, gel-purified DNA inserts as described (Cairo et al, 1992). Due to a certain variability in transfer efficiency, specific activity of probes, and times of exposure, a sample with RNA from liver of an untreated rat was included in each blot.…”

Estrogen‐regulated expression of a growth arrest specific gene (gas‐1) in rat uterus

“…One of these genes, gas-I, in addition to the growth dependent behaviour characteristic of the gas gene family, seems to have also an active role in growth suppression (Del Sal et al, 1992). While the expression of the gas genes in response to growth 1065-6995/93/090857-06/$08.00/0 variations in cell cultures has been well documented (Schneider et al, 1988;Ciccarelli et al, 1990;Manfioletti et al, 1990;Coccia et al, 1992;Brancolini et al, 1992), their regulation in vivo received less attention (Welcher et al, 1991;Spreyer et al, 1991;Cairo et al, 1992).…”

Suppression of ras oncogene-mediated transformation

“…SV40 transformed NIH/3T3 cells were insensitive toward gas-I inhibition. Reduced expression of gas-1 was reported in Ki-ras transformed NIH/3T3 cells and primary mouse fibroblasts (Cairo et al 1992). However, high levels of gas-1 mRNA were detected in rapidly proliferating fibrosarcoma and rhabdomyosarcoma maintained as xenografts on syngeneic mice.…”