Relationship between metastatic ability and H-ras oncogene expression in rat mammary cancer cells transfected with the v-H-ras oncogene.
To study the relationship between metastatic ability and activated ras expression, a cloned, low metastatic, dimethylbenz(a)anthracene-induced rat mammary cancer cell line (RMC1) was transfected with the v-H-ras oncogene. Cloned transfectants were characterized as high, medium, or low expressors of the v-H-ras gene, on the basis of Southern, Northern, and Western blot analysis. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors; however, the in vivo growth rate of cloned transfectants which expressed any level of v-H-ras oncogene was significantly higher (approximately 5-fold) than that observed in the untransfected RMC1 cells. Control (neo only) transfectants exhibited no change in growth rate and had a low metastatic ability comparable to that of the parental untransfected cells. Certain cloned v-H-ras expressing transfectants were highly metastatic to the lungs and lymph nodes. These highly metastatic H-ras transfectants differed widely however, in their level of H-ras expression. The lung colonization potential following i.v. inoculation was increased in all transfectants which expressed any level of v-H-ras gene. These studies suggest that while v-H-ras transfection can result in the development of metastatic ability in rat mammary cancer cells, there is no simple dose-response relationship between the level of v-H-ras expression in cloned rat mammary cancer cell transfectants and the development of experimental or spontaneous metastases.
Kyprianou
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N
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231.
Isaacs
J T
JT
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015139:Blotting, Southern; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D011919:Rats, Inbred Strains; D014162:Transfection
D011518:Proto-Oncogene Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene; D016283:Proto-Oncogene Proteins p21(ras)