The ability of rasH genes to induce metastatic potential as well as transformation and tumorigenicity was demonstrated in several cell types. NIH-3T3 cells transformed with either the DNA of the Harvey Sarcoma Virus or with the cloned T24 human rasH oncogene resulted in cells which formed lung metastases. Early passage diploid rat embryo fibroblasts transformed by rasH were also metastatic as were early passage Chinese hamster lung fibroblasts transformed by rasH. Thus, the rasH oncogenes can induce metastatic behavior even in diploid fibroblasts. However, transformation itelf or the ability to grow as a tumor was shown to be insufficient to result in metastasis. The normal cellular counterpart of the rasH oncogene can also transform NIH-3T3 cells if an LTR is placed upstream from the c-rasH gene to increase the levels of the normal P21. The NIH-3T3 cells transformed by this construction, while highly tumorigenic, do not metastasize. RasH did not induce metastatic potential in all recipient cell lines tested. For example C127 cells, a murine epithelioid line which were transformed by rasH, did not metastasize although morphologically transformed and highly tumorigenic. The induction of metastatic potential in those cells is being attempted in gene transfer experiments.
