Miyado K, Kimura M, Taniguchi S
Molecular Medicine Research Center, Tokai University, Isehara, Japan.
Biochem Biophys Res Commun. 1996 Aug 14;225(2):427-35. doi: 10.1006/bbrc.1996.1190.
Tropomyosin is an actin-associated cytoskeletal protein expressed in muscle and non-muscle cells. There are several tropomyosin isoforms, and their cellular expression is known to be associated with transformation events caused by retroviral infection and chemical mutagens. We found that expression of a low-molecular weight tropomyosin isoform, TM5/TM30nm, was higher in a high-metastatic B16 mouse melanoma cell line, B16-F10, than in B16-F1, a low-metastatic mouse melanoma cell line. In order to determine whether this elevated level of TM5/TM30nm plays a role in malignant phenotype, B16-F10 cells were transfected with recombinant DNA containing antisense rat TM5/TM30nm cDNA linked to the human metallothioneinIIa promoter, which is inducible by heavy metals such as zinc and cadmium. When the stably transfected clones were treated with ZnSO4, decreased expression of TM5/TM30nm and reduction in cell motility, which is thought to be an indicator of cellular malignancy were observed. These findings suggest that TM5/TM30nm plays a fundamental role in regulating cell motility, which is essential for metastasis and invasion of tumor cells.
原肌球蛋白是一种与肌动蛋白相关的细胞骨架蛋白，在肌肉细胞和非肌肉细胞中均有表达。存在多种原肌球蛋白同工型，已知它们在细胞中的表达与逆转录病毒感染和化学诱变剂引起的转化事件有关。我们发现，低分子量原肌球蛋白同工型TM5/TM30nm在高转移性B16小鼠黑色素瘤细胞系B16-F10中的表达高于低转移性小鼠黑色素瘤细胞系B16-F1。为了确定TM5/TM30nm水平的升高是否在恶性表型中起作用，用含有与人类金属硫蛋白IIa启动子相连的反义大鼠TM5/TM30nm cDNA的重组DNA转染B16-F10细胞，该启动子可被锌和镉等重金属诱导。当用硫酸锌处理稳定转染的克隆时，观察到TM5/TM30nm的表达降低以及细胞运动性降低，细胞运动性被认为是细胞恶性程度的一个指标。这些发现表明，TM5/TM30nm在调节细胞运动性中起重要作用，而细胞运动性对于肿瘤细胞的转移和侵袭至关重要。
