V-MOS-TRANSFORMED CELLS FAIL TO ENTER QUIESCENCE BUT GROWTH ARREST ING1 FOLLOWING SERUM WITHDRAWAL

The product of the mos protooncogene normally functions in the inducti on of meiosis and regulation of cell-cycle progression in oocytes. Her e we have investigated the cell-cycle progression of NIH3T3 cells tran sformed by the v-mos gene. Flow cytometric analysis showed that logari thmically growing v-mos-transformed cells do not differ from their non transformed counterparts in the distribution of cells in the G1, S, an d G2/M phases. Likewise, after serum withdrawal for 48 h, both normal and v-mos-transformed NIH3T3 cells have essentially ceased proliferati on, as analyzed by flow cytometry, [H-3]thymidine and BrdU incorporati on into newly synthesized DNA, and mitotic indexes. However, while the normal NIH3T3 cells are arrested in a quiescent state, the v-mos-tran sformed cells are arrested in early to mid G1, prior to the point wher e cells require certain amino acids for proliferation (V point). In ag reement with these different arrest points, the v-mos-transformed cell s enter 8 phase following serum stimulation within about 8 h, without the additional 4-to 6-h lag period characteristically displayed by the parental NIH3T3 cells. In addition, we show a lack of expression of a growth arrest-specific gene product, gas1, in the serum-arrested v-mo s-transformed cells. These data demonstrate that v-mos-transformed cel ls display growth characteristics that differ fundamentally from those of normal cells or cells transformed by overexpression of nye [1]. Ou r results suggest that the v-mos oncoprotein transforms cells, at leas t in part, by preventing exit from the cell cycle into quiescence. (C) 1994 Academic Press, Inc.