Alteration of the tumorigenic and metastatic properties of neoplastic cells is associated with the process of calcium phosphate-mediated DNA transfection.
Alteration of the tumorigenic and metastatic properties of neoplastic cells is associated with the process of calcium phosphate-mediated DNA transfection.
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肿瘤细胞致瘤和转移特性的改变与磷酸钙介导的 DNA 转染过程有关。
DOI：
10.1073/pnas.84.5.1263
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发表时间：
1987
影响因子：
11.1
通讯作者：
Breitman,ML
中科院分区：
文献类型：
--
作者：
Kerbel,RS;Waghorne,C;Man,MS;Elliott,B;Breitman,ML
在设计评估人Ha-ras基因表达对转染小鼠肿瘤细胞恶性行为的影响的研究过程中，我们注意到Ca 3（PO 4）2介导的DNA转染过程本身与肿瘤发生或转移行为的深刻改变有关。用作这些研究受体的细胞系是称为SP1的致瘤性非转移性CBA/J小鼠乳腺腺癌细胞系。当用含有neo基因（pSV 2neo）和活化的Ha-ras基因（pT 24-c3）的质粒共转染时，来自合并的（5-10个集落）G418抗性集落的细胞在皮下接种后在85%的小鼠中引起自发性肺转移。然而，我们注意到17%的接种G418抗性pSV 2neo转染的SP1细胞的对照小鼠也有肺转移，并且由于接种物包含更大的库大小（50-100个集落），该数字接近100%。当检查从分离的pSV 2neo转染集落建立的细胞系时，发现3/16是转移性的。我们还发现，3/16克隆生长缓慢，或根本没有，在CBA/J小鼠，而他们在无胸腺（裸）小鼠生长迅速。这些后者的克隆中的三分之二的免疫原性的增加伴随着I类H-2Dk主要组织相容性复合物抗原的表达，这在亲本SP1细胞中是检测不到的。这些结果中的至少一些似乎是由于单独暴露于Ca 3（PO 4）2，因为我们发现其导致5/20（25%）的克隆表现出转移特性。我们的研究结果表明，遗传性的恶性行为的转染肿瘤细胞的变化，可以观察到在高频率的Ca 3（PO 4）2介导的DNA转染的过程后，这些变化可能带来的部分遗传干扰受体细胞基因的表达。
During the course of studies designed to assess the effect of human Ha-ras gene expression on the malignant behavior of transfected mouse tumor cells we noted that the process of Ca3(PO4)2-mediated DNA transfection was itself associated with profound alterations in tumorigenic or metastatic behavior. The cell line used as a recipient for these studies was a tumorigenic nonmetastatic CBA/J mouse mammary adenocarcinoma line called SP1. When cotransfected with plasmids containing the neo gene (pSV2neo) and the activated Ha-ras gene (pT24-c3), cells from the pooled (5-10 colonies) G418-resistant colonies gave rise to spontaneous lung metastases in 85% of mice after subcutaneous inoculation. However, we noted that 17% of control mice inoculated with G418-resistant pSV2neo-transfected SP1 cells also had lung metastases and that this number approached 100% as the inoculum comprised a greater pool size (50-100 colonies). When cell lines established from isolated pSV2neo-transfected colonies were examined, 3/16 were found to be metastatic. We also found that 3/16 clones grew slowly, or not at all, in CBA/J mice, whereas they grew readily in athymic (nude) mice. The increase in immunogenicity of two out of three of these latter clones was accompanied by expression of the class I H-2Dk major histocompatibility complex antigen that was not detectable in the parental SP1 cells. At least some of these results would appear to be due to exposure to Ca3(PO4)2 alone, as we found that it resulted in 5/20 (25%) clones manifesting metastatic properties. Our results suggest that heritable changes in malignant behavior of transfected tumor cells can be observed at high frequency subsequent to the process of Ca3(PO4)2-mediated DNA transfection, and these changes may be brought about in part by inherited disturbances in expression of recipient cell genes.