Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene

Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene
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DOI:
10.1038/sj.onc.1201648
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发表时间:
1998-03-19
期刊:
影响因子:
8
通讯作者:
Imai, K
Imai, K
中科院分区:
医学1区
文献类型:
--
作者:
Takaoka, A;Hinoda, Y;Imai, K

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KA 11是一个潜在的前列腺癌转移抑制基因。我们用北方杂交分析发现,10个胃癌和结肠癌细胞系中有6个(60%)KA 11 mRNA表达水平为阴性或极低。因此,通过使用两种稳定的转染子,即,转染反义KA 11 cDNA抑制KA 11 mRNA表达的BM 314细胞的反义转染子和转染正义cDNA增强KA 11 mRNA表达的DLD-1细胞的正义转染子。结果表明:(1)KA 11基因的表达对结肠癌BM 314和DLD-1细胞的体外生长率无明显影响,(2)细胞聚集实验表明KA 11能增强结肠癌细胞的非钙依赖性聚集能力;(3)通过细胞运动性和侵袭性测定显示,KA 11抑制这些细胞的运动性和体外侵袭性,以及(4)此外,KA 11的表达抑制了结肠癌细胞与纤连蛋白的结合和在纤连蛋白包被的平板上的迁移,这表明KA 11基因表达的降低可能有助于结肠癌细胞的侵袭和转移能力。
KA11 is a potential metastatic suppressor gene for prostate cancer, We found by Northern blot analysis that six of ten (60%) gastric and colon cancer cell lines exhibited undetectable or very low expression level of KA11 mRNA. The effects of KA11 on the adhesion, motility and invasiveness of colon cancer cells was therefore investigated by using two kinds of stable transfectants, i.e., antisense transfectants of BM314 cells whose KA11 mRNA expression was suppressed by transfer of antisense KA11 cDNA and sense transfectants of DLD-1 cells with the enhanced KA11 mRNA by sense cDNA transfer. The following results were obtained: (1) KA11 gene expression had no significant effect on in vitro cell growth rate of colon cancer BM314 and DLD-1 cells; (2) Cell aggregation assay showed that KA11 enhanced the Ca++-independent aggregatability of those colon cancer cells; (3) It was revealed by cell motility and invasion assays that KA11 suppressed both the motility and in vitro invasiveness of those cells and (4) Furthermore, both the binding to fibronectin and the migration on fibronectin-coated plates of those cells were inhibited by KA11 expression, These suggest that reduced KA11 gene expression may contribute to the invasiveness and metastatic ability of colon cancer cells.