c-fos transfection of 3LL tumor cells turns on MHC gene expression and consequently reduces their metastatic competence.
Transfection with c-fos genes of cells of a highly metastatic (H-2K- H-2D+) clone, DI22, of the 3LL carcinoma, causes activation of H-2K gene expression. Experiments were carried out to test whether these transfectants exhibit reduced metastatic competence. Studying II mouse c-fos, 6 mouse c-fos and 2 v-fos transfected clones, we observed that clones expressing high steady-state levels of the fos mRNA also expressed elevated levels of H-2K and H-2D mRNA, and high levels of cell-surface H-2K and H-2D glycoproteins. The transfectants were tested for generation of spontaneous metastasis following intra-footpad inoculation of the tumor cells. Clones expressing high levels of fos and of H-2 antigens, particularly those expressing high levels of cell-surface H-2Kb molecules, showed a reduction of their metastatic competence. Statistical analysis revealed that c-fos transfectants are significantly less metastatic than the parental cells. The molecular mechanisms of c-fos activation of H-2 genes is briefly discussed.
Kushtai
G
G
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Feldman
M
M
Eisenbach
L
L
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000276:immunology; D005805:Genes, MHC Class I / Q000235:genetics* / Q000276:immunology; D006183:H-2 Antigens / Q000032:analysis / Q000235:genetics; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D014162:Transfection / Q000235:genetics* / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D006183:H-2 Antigens; D012333:RNA, Messenger