Growth control in mouse Y-1 adrenocortical tumor cells: role of c-Ki-ras amplification and effects of ACTH.

Abstract

Even though the proto-oncogene c-Ki-ras is found to be amplified and overexpressed in the malignant Y-1 mouse corticoadrenal cell line, evidence for a causal relationship between c-Ki-ras overexpression and malignancy is still lacking. Such evidence is presented in this report. Amplified c-Ki-ras was found in both sublines of Y-1 cells that carry DM (double minute) or HSR (homogeneously stained region) chromosomes. Y-1 normal revertants did not display c-Ki-ras amplified sequences. Spontaneous retransformation of the normal revertants yielded anchorage-independent non-tumorigenic cells in which c-Ki-ras was not amplified. We propose that c-Ki-ras amplification is required to maintain the malignant state of Y-1 cells. Constitutive expression of poly A RNA homologous to viral sequences were detected in all sublines of Y-1 cells (malignant or normal revertants) by Northern hybridization using probes derived from the pFBJ-2 provirus. Rapid induction of c-fos proto-oncogene mRNA and late reduction in the levels of poly A+ viral transcripts resulted from ACTH treatment of Y-1 cells. However, ACTH treatment did not change c-Ki-ras mRNA levels.