Oncogene addiction is a cellular property by which cancer cells become highly dependent on the expression of oncogenes for their survival. Oncogene addiction can be exploited to design molecularly targeted drugs that kill only cancer cells by inhibiting the specific oncogenes. Genes and cell lines exhibiting oncogene addiction, as well as the mechanisms by which cell death is induced when addicted oncogenes are suppressed, have been extensively studied. However, it is still not fully understood how oncogene addiction is acquired in cancer cells. Here, we take a synthetic biology approach to investigate whether oncogenic mutation or oncogene expression suffices to confer the property of oncogene addiction to cancer cells. We employed human mammary epithelium-derived MCF-10A cells expressing the oncogenic KRAS or BRAF. MCF-10A cells harboring an oncogenic mutation in a single-allele of KRAS or BRAF showed weak tumorigenic activity, but no characteristics of oncogene addiction. MCF-10A cells overexpressing oncogenic KRAS demonstrated the tumorigenic activity, but MCF-10A cells overexpressing oncogenic BRAF did not. Neither cell line exhibited any oncogene addiction properties. These results indicate that the introduction of oncogenic mutation or the overexpression of oncogenes is not sufficient for cancer cells to acquire oncogene addiction, and that oncogene addiction is not associated with tumorigenic potential.

中文翻译：

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致癌性KRAS或BRAF的致癌突变或过表达不足以赋予致癌基因成瘾作用。

癌基因成瘾是一种细胞特性，癌细胞可以通过这种特性高度依赖癌基因的表达来维持生存。可以利用致癌基因上瘾来设计分子靶向药物，从而通过抑制特定的致癌基因而仅杀死癌细胞。已经广泛研究了显示致癌基因成瘾的基因和细胞系，以及抑制成瘾的致癌基因时诱导细胞死亡的机制。然而，仍未完全了解癌细胞中如何获得致癌基因成瘾。在这里，我们采用一种合成生物学方法来研究致癌突变或致癌基因表达是否足以赋予致癌基因上瘾的癌细胞特性。我们采用了人类乳腺上皮来源的表达致癌性KRAS或BRAF的MCF-10A细胞。在KRAS或BRAF的单个等位基因中具有致癌突变的MCF-10A细胞显示出较弱的致瘤活性，但没有致癌基因成瘾的特征。过度表达致癌KRAS的MCF-10A细胞表现出致癌活性，而过度表达致癌BRAF的MCF-10A细胞则没有。两种细胞系均未表现出任何癌基因成瘾特性。这些结果表明，致癌突变的引入或致癌基因的过表达不足以使癌细胞获得致癌基因成瘾，并且致癌基因成瘾与致癌潜力无关。但是过表达致癌BRAF的MCF-10A细胞却没有。两种细胞系均未表现出任何癌基因成瘾特性。这些结果表明，致癌突变的引入或致癌基因的过表达不足以使癌细胞获得致癌基因成瘾，并且致癌基因成瘾与致癌潜力无关。但是过表达致癌BRAF的MCF-10A细胞却没有。两种细胞系均未表现出任何癌基因成瘾特性。这些结果表明，致癌突变的引入或致癌基因的过表达不足以使癌细胞获得致癌基因成瘾，并且致癌基因成瘾与致癌潜力无关。