Methionine-independence, tumorigenicity and oncogene expression of rat hepatocarcinoma cells

Methionine-dependent (Met-Hcy+) revertant sublines were isolated from a methionine-independent (Met+Hcy-) rat hepatocarcinoma cell line (LF). Characterization of these sublines has shown that long-term culture in methionine-deprived medium significantly decreases their ability to grow in vitro, their tumorigenicity in new-born syngeneic animals and their level of transcription of 3 oncogenes (c-Ki-ras, c-Ha-ras, c-myc) involved in hepatic growth. These data strongly support a relationship between methionine-dependence and ability to grow in vivo as tumors. A shift in methionine-supplemented medium for several cell generations of the various sublines grown in methionine deprived medium, has revealed that under these conditions, the cells maintain a diminished in vitro growth and tumorigenic capacity, despite an increased transcription of c-Ki-ras, c-Ha-ras and c-myc. This points out the complexity of the relationship between the level of activity of some oncogenes and the expression of the malignant phenotypes.