REDUCED TUMOR-INCIDENCE, METASTATIC POTENTIAL, AND CYTOKINE RESPONSIVENESS OF NM23-TRANSFECTED MELANOMA-CELLS
REDUCED TUMOR-INCIDENCE, METASTATIC POTENTIAL, AND CYTOKINE RESPONSIVENESS OF NM23-TRANSFECTED MELANOMA-CELLS
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DOI：
10.1016/0092-8674(91)90404-m
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发表时间：
1991-04-05
期刊：
影响因子：
64.5
通讯作者：
STEEG, PS
中科院分区：
文献类型：
--
作者：
LEONE, A;FLATOW, U;STEEG, PS
在某些啮齿动物模型系统和人乳腺肿瘤中nm 23基因表达的降低与高肿瘤转移潜力相关。 为了研究nm 23表达的功能效应，我们将组成型小鼠nm 23 -1表达构建体转染到高转移性K-1735 TK小鼠黑色素瘤细胞中。 与对照转染的TK克隆相比，表达外源性nm 23 -1构建体的TK克隆表现出原发性肿瘤形成的发生率降低，肿瘤转移潜能显著降低，与肿瘤细胞生长无关，并且在软琼脂定殖试验中对细胞因子转化生长因子-β-1的反应改变。 相反，nm 23 -1转染的TK克隆在内在肿瘤细胞生长方面没有表现出显著差异，即，体内原发性肿瘤大小、体外贴壁依赖性生长速率和体外软琼脂中贴壁非依赖性集落形成。 这些数据证明了nm 23对癌症过程的几个方面的抑制作用，包括肿瘤转移。
Reduced expression of the nm23 gene in certain rodent model systems and human breast tumors has been correlated with high tumor metastatic potential. To investigate the functional effects of nm23 expression, we have transfected a constitutive murine nm23-1 expression construct into highly metastatic K-1735 TK murine melanoma cells. TK clones expressing the exogenous nm23-1 construct exhibited a reduced incidence of primary tumor formation, significant reductions in tumor metastatic potential independent of tumor cell growth, and altered responses to the cytokine transforming growth factor-beta-1 in soft agar colonization assays, compared with control-transfected TK clones. In contrast, nm23-1-transfected TK clones exhibited no significant differences in intrinsic tumor cell growth, i.e., primary tumor size in vivo, anchorage-dependent growth rate in vitro, and anchorage-independent colony formation in soft agar in vitro. The data demonstrate a suppressive effect of nm23 on several aspects of the cancer process, including tumor metastasis.