Suppression of neoplastic transformation and regulation of cytoskeleton bytropomyosins

Down regulation of Tropomyosins (TMs) is a consistent biochemical change ob served in many transformed cells. Our previous work has demonstrated that T ropomyosin-1 is an antioncogene and it is a class II tumor suppressor. Usin g ras-transformed murine fibroblasts (DT cells), we have examined the effec ts of co-expression of two isoforms of TM on cell morphology: cytoskeleton and tumorigenecity. Enhanced expression of TMI, a suppressor of transformat ion, along with TM2 which is not a tumor suppressor results in the formatio n of well-organized microfilaments, a morphology that resembles normal fibr oblasts, and suppression of tumorigenecity. Tumor formation in vivo was com patible with the persistence of high-level of TM2, brit not TMI. Homodimers of TM1 and TM2 were observed in these cells, Thus, restoration of expressi on of TM1 and TM2 protein in ras-transformed cells suppresses the transform ed phenotype with dramatic re-organization of microfilaments. These data sh ow thar TM2 cooperates with TMI in the reorganization of microfilaments, wh ile TM1 is a suppressor of the transformed phenotype.