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 subB- cells. To examine the possibility of a direct relationship between TM-1 expression and the subB- phenotype, subB+ 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.
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
J
J
Boyd
J I
JI
Risinger
R W
RW
Wiseman
B A
BA
Merrick
J K
JK
Selkirk
J C
JC
Barrett
D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000235:genetics*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D003599:Cytoskeleton / Q000648:ultrastructure; D015342:DNA Probes; D029721:Drosophila Proteins; D015180:Electrophoresis, Gel, Two-Dimensional; D004622:Embryo, Mammalian / Q000166:cytology; D016147:Genes, Tumor Suppressor; D014644:Genetic Variation; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016372:RNA, Antisense; D011994:Recombinant Proteins / Q000096:biosynthesis; D014335:Tropomyosin / Q000096:biosynthesis / Q000235:genetics*
D015342:DNA Probes; D029721:Drosophila Proteins; D016372:RNA, Antisense; D011994:Recombinant Proteins; C097163:Tm2 protein, Drosophila; D014335:Tropomyosin