We have continued our studies on the relationship of suppression of tropomyosin (TM) synthesis to neoplastic transformation. Previous observations have led us to hypothesize that: a.) TM suppression is a causal event in neoplastic transformation; and b.) the oncogenic pathways initiated by a number of different oncogenes and other modalities converge on and act through TM suppression will lead to a reduction in neoplastic characteristics of cells transformed by modalities that suppress TM expression. To test this prediction, we have used a retroviral expression vector to insert a full-length cDNA encoding human TM1 into the v-Ki-ras transformed cell line DT. The technique proved to have been effective in restoring high levels of expression of TM1 mRNA and protein. Anchorage independent growth in semi-solid agar was virtually eliminated in the TM1 expressing cells. Tumorigenesis in athymic mice was also markedly reduced and when tumors did form, they were found no longer to express the 2.0 kB inserted TMe1 mRNA. Thus, cells with restored TM1 expression did not produce tumors. These results are strong evidence that TM suppression plays a necessary causal role in the production by the ras oncogene of those components of the transformed phenotype that closely correlate with neoplastic potential: anchorage independence and tumorigenesis in athymic mice. Since many other oncogenic modalities induce TM suppression, it is likely that those modalities also depend on this pathway for transformation. TM suppression thus emerges as a major common step in oncogenesis by many agents.
