Boyd J, Risinger J I, Wiseman R W, Merrick B A, Selkirk J K, Barrett J C
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11534-8. doi: 10.1073/pnas.92.25.11534.
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.
对化学永生化的叙利亚仓鼠胚胎细胞的变体进行了亚克隆，这些变体在与纤维肉瘤细胞系杂交时，要么保留了（supB+），要么失去了（supB-）抑制肿瘤发生的能力。两种supB细胞类型均无致瘤性；然而，supB-细胞而非supB+细胞表现出条件性非贴壁生长。在supB-细胞而非supB+细胞中观察到肌动蛋白微丝组织的改变，这与supB-细胞中肌动蛋白结合蛋白原肌球蛋白1（TM-1）的显著减少相对应。为了研究TM-1表达与supB-表型之间直接关系的可能性，用含有反义方向TM-1 cDNA的表达载体转染supB+细胞。反义诱导的supB+克隆中TM-1水平降低导致微丝重组，并赋予了与supB-细胞特征无法区分的非贴壁生长潜能。这些数据提供了直接证据，表明TM-1调节微丝组织和非贴壁生长，并表明微丝改变足以实现非贴壁生长。
