Association in the Expression of Kirsten-ras Oncogene and the Major Histocompatibility Complex Class I Antigens in Fibrosarcoma Tumor Cell Variants Exhibiting Different Metastatic Capabilities

The metastatic properties of the methylcholanthrene-induced T-10 sarcoma tumor variants which originated in C3H x C57B1/6 F₁mice are correlated with the relative expression of class I major histocompatibility complex antigens. Both the nonmetastatic and the highly metastatic clones were found to lack the H-2K region-controlled H-2K^band H-2K^kantigens. However, the nonmetastatic clones express only the H-2D^bmolecule whereas the metastatic clones express both the H-2D^band the H-2D^kmolecules. Transfection of the highly metastatic lines with cloned H-2K genes (K^b, K^k) reduced their tumorigenicity and abolished the formation of metastatis in syngeneic mice, while the transfection of the nonmetastatic lines with cloned H-2D^k, genes resulted in shifting the cells to the metastatic phenotype. The present study is aimed to investigate the expression of protooncogenes in the T-10 fibrosarcoma lines that exhibit distinct metastatic properties in correlation with the expressed H-2 antigens. The major oncogene which showed differential expression in the T-10 clones is Ki-ras. The amounts of specific Ki-ras messenger RNA and the Ki-ras M_r 21, 000 protein are expressed in elevated levels in the H-2D^k-negative nonmetastatic clones in comparison with a low level of expression in the H-2D^k-positive highly metastatic clones. Expression of H-2K antigens following transfection with cloned H-2K genes had no effect on the expressed Ki-ras oncogene in the T-10 clones. However, transfection of the nonmetastatic cells with the cloned H-21^k gene resulted in shifting of the cells to a highly metastatic phenotype and in reduction of the expressed c-Ki-ras oncogene.