CLUSTERING OF DISCRETE CELL PROPERTIES ESSENTIAL FOR TUMORIGENICITY AND METASTASIS .3. DISSOCIATION OF THE PROPERTIES IN N-RAS-TRANSFECTED RSV-SR-TRANSFORMED CELLS

We have previously shown that RSV-SR-transformed hamster cells acquire high resistance to H2O2, i.e. the cytotoxic product of activated macrophages (H2O2R) and that they begin to secrete PGE (PGE(s)), thus inactivating the CTA of NK cells. Among normal cells, the same phenotype is expressed in activated macrophages. In all our RSV-transformed cells these 2 properties were jointly expressed and correlated with high tumorigenicity and experimental metastasizing of these cells. We now show that transfection of 3 RSV-SR-transformed cell strains with activated N-ras leads either to complete inhibition of the H2O2R + PGE(s) phenotype in all clones of one strain, or to inhibition of PGE(s) only in the majority of clones of 2 other strains. Unexpectedly, the complete or partial inhibition of this phenotype did not alter the high tumorigenicity of 2 strains of these cells, but lower tumorigenicity was evident in almost all clones of the third strain (as well as in some gene-neo-transfected clones of these strains). The loss of PGE(s) made these cells susceptible to the CTA of NK cells, while the loss of H2O2R did not alter their resistance to the CTA of macrophages. Expression of the H2O2R + PGE(s) phenotype was retained in all cloned variants of control, gene-neo-transfected cells. The possible relation of the N-ras gene to regulation of src gene activities in RSV-SR-transformed cells is discussed.