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.

Abstract

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.

• Authors: Y Alon, G J Hammerling, S Segal, M Bar-Eli
• Journal: Cancer research (Cancer Res) Vol. 47 Issue 10 Pg. 2553-7 (May 15 1987) ISSN: 0008-5472 [Print] United States
• PMID: 3552201 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• H-2 Antigens
• Histocompatibility Antigens Class II
• Methylcholanthrene

Topics

• Animals
• Clone Cells
• Fibrosarcoma (genetics)
• Gene Expression Regulation
• H-2 Antigens (genetics)
• Histocompatibility Antigens Class II (genetics)
• Immunosorbent Techniques
• Kirsten murine sarcoma virus (genetics)
• Methylcholanthrene
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Neoplasm Metastasis (genetics)
• Oncogenes
• Proto-Oncogenes
• Rats
• Sarcoma, Experimental (chemically induced)
• Transfection