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. We have obtained evidence supporting this hypothesis by restoring expression of TM1, one of two suppressed tropomyosins in the v-Ki-ras transformed NIH3T3 cell line, DT, through the use of a retroviral vector (pBNC) carrying a full length cDNA encoding human TM1. Cell clones expressing the cDNA had elevated levels of TM1 and lost the ability to grow under anchorage-independent conditions. They also did not participate in formation of tumors in athymic mice. The ability of elevated levels of TM in the transduced clones to be utilized in the cytoskeleton is under study, as is their participation in the formation of the physiological dimers in which TM occurs in vivo. Complete reversal of the transformed phenotype may require simultaneous restoration of both TM1 and TM2 to permit formation of hereodimeric TM molecules, which are the preferred form in vivo. Materials for the insertion of TM2-encoding cDNA into clones already restored in TM1 expression are now being prepared. TM1 expression has also been restored in the human breast cancer cell line, MCF-7, which we previously showed to be defective in synthesis of this TM isoform. Testing for effects of this restoration on the neoplastic phenotype is currently in progress.
