Suppression of neoplastic transformation and regulation of cytoskeleton by tropomyosins.

Abstract

Down regulation of Tropomyosins (TMs) is a consistent biochemical change observed in many transformed cells. Our previous work has demonstrated that Tropomyosin-1 is an antioncogene and it is a class II tumor suppressor. Using ras-transformed murine fibroblasts (DT cells), we have examined the effects of co-expression of two isoforms of TM on cell morphology, cytoskeleton and tumorigenecity. Enhanced expression of TM1, a suppressor of transformation, along with TM2 which is not a tumor suppressor results in the formation of well-organized microfilaments, a morphology that resembles normal fibroblasts, and suppression of tumorigenecity. Tumor formation in vivo was compatible with the persistence of high-level of TM2, but not TM1. Homodimers of TM1 and TM2 were observed in these cells. Thus, restoration of expression of TM1 and TM2 protein in ras-transformed cells suppresses the transformed phenotype with dramatic re-organization of microfilaments. These data show that TM2 cooperates with TM1 in the reorganization of microfilaments, while TM1 is a suppressor of the transformed phenotype.