REGULATION OF MICROFILAMENT ORGANIZATION AND ANCHORAGE-INDEPENDENT GROWTH BY TROPOMYOSIN-1

Variants of chemically immortalized Syrian hamster embryo cells that had either retained (supB(+)) or lost (supB(-)) the ability to suppress tumorigenicity when hybridized with a fibrosarcoma cell line were subcloned. Both supB cell types are nontumorigenic; however, the supB(-) but not supB(+) cells exhibit conditional anchorage-independent growth. Alterations of actin microfilament organization were observed in supB(-) but not supB(+) cells that corresponded to a significant reduction of the actin-binding protein tropomyosin 1 (TM-1) in supB(-) cells. To examine the possibility of a direct relationship between TM-1 expression and the supB(-) phenotype, supB(+) cells were transfected with an expression vector containing the TM-1 cDNA in an antisense orientation. The antisense-induced reduction of TM-1 levels in supB(+) clones caused a microfilament reorganization and conferred anchorage-independent growth potential that were indistinguishable from those characteristic of supB(-) cells. These data provide direct evidence that TM-1 regulates both microfilament organization and anchorage-independent growth and suggest that microfilament alterations are sufficient for anchorage-independent growth.