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 S-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.