Suppression of neoplastic transformation and regulation of cytoskeleton by tropomyosins.
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.
Shah
V
V
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Braverman
R
R
Prasad
G L
GL
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003599:Cytoskeleton / Q000473:pathology / Q000502:physiology*; D029721:Drosophila Proteins; D016147:Genes, Tumor Suppressor; D051379:Mice; D020033:Protein Isoforms / Q000096:biosynthesis / Q000502:physiology; D014335:Tropomyosin / Q000096:biosynthesis / Q000502:physiology
D000970:Antineoplastic Agents; D029721:Drosophila Proteins; D020033:Protein Isoforms; C097163:Tm2 protein, Drosophila; C490774:Tpm1 protein, mouse; D014335:Tropomyosin