EXPRESSION OF TRANSDUCED TROPOMYOSIN-1 CDNA SUPPRESSES NEOPLASTIC GROWTH OF CELLS TRANSFORMED BY THE RAS ONCOGENE

Synthesis of certain members of the tropomyosin family of microfilamen t-associated proteins is suppressed in fibroblasts neoplastically tran sformed by a number of retroviral oncogenes, by transforming growth fa ctor a, and by chemical mutagens. To test whether tropomyosin suppress ion is a required event in neoplastic transformation, expression of on e of two suppressed tropomyosins in NIH 3T3 mouse cells transformed by the ras oncogene was restored by retro-virally mediated cDNA transfer . Cells expressing the inserted cDNA showed partial restoration of mic rofilament bundle formation (which is typically deranged in transforme d cells) together with increased cytoplasmic spreading. More important ly, they lost anchorage-independent growth capability, and the onset o f tumor growth in athymic mice was delayed. When tumors arose they no longer expressed the inserted cDNA. These observations support the con clusion that tropomyosin suppression is a necessary event for the expr ession of components of the transformed phenotype, particularly with r espect to anchorage-independent growth and tumorigenesis, which correl ate closely with neoplastic potential. This potentially reversible req uirement may link different initial events produced by a variety of on cogenic modalities to a common pathway leading to neoplastic growth.