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 C57Bl/6 F1 mice 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-2Kb and H-2Kk antigens. However, the nonmetastatic clones express only the H-2Db molecule whereas the metastatic clones express both the H-2Db and the H-2Dk molecules. Transfection of the highly metastatic lines with cloned H-2K genes (Kb, Kk) reduced their tumorigenicity and abolished the formation of metastasis in syngeneic mice, while the transfection of the nonmetastatic lines with cloned H-2Dk 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 Mr 21,000 protein are expressed in elevated levels in the H-2Dk-negative nonmetastatic clones in comparison with a low level of expression in the H-2Dk-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-2Dk gene resulted in shifting of the cells to a highly metastatic phenotype and in reduction of the expressed c-Ki-ras oncogene.
D000818:Animals; D002999:Clone Cells; D005354:Fibrosarcoma / Q000235:genetics*; D005786:Gene Expression Regulation; D006183:H-2 Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007163:Immunosorbent Techniques; D007708:Kirsten murine sarcoma virus / Q000235:genetics; D008748:Methylcholanthrene; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000235:genetics*; D009857:Oncogenes; D011519:Proto-Oncogenes; D051381:Rats; D012513:Sarcoma, Experimental / Q000139:chemically induced; D014162:Transfection
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D008748:Methylcholanthrene