Oncogenic mutation or overexpression of oncogenic KRAS or BRAF is not sufficient to confer oncogene addiction.
Oncogenic mutation or overexpression of oncogenic KRAS or BRAF is not sufficient to confer oncogene addiction.
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DOI：
10.1371/journal.pone.0249388
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Aoki K
中科院分区：
文献类型：
--
作者：
Ito RE;Oneyama C;Aoki K
癌基因成瘾是癌细胞高度依赖癌基因表达生存的一种细胞特性。癌基因成瘾可以用来设计分子靶向药物，通过抑制特定的癌基因来杀死癌细胞。表现出癌基因成瘾的基因和细胞系，以及当成瘾癌基因被抑制时诱导细胞死亡的机制，已经被广泛研究。然而，人们仍然不完全了解癌基因成瘾是如何在癌细胞中获得的。在这里，我们采用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癌细胞致癌基因成瘾的特性。我们使用表达致癌KRAS或BRAF的人乳腺上皮源性MCF-10A细胞。含有KRAS或BRAF单等位基因致癌突变的MCF-10A细胞表现出较弱的转化活性，但没有致癌基因成瘾的特征。过表达致癌KRAS的MCF-10A细胞表现出转化活性，而过表达致癌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，致癌突变的引入或癌基因的过度表达不足以使细胞获得癌基因成瘾，并且癌基因成瘾与转化活性无关。
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 transformation activity, but no characteristics of oncogene addiction. MCF-10A cells overexpressing oncogenic KRAS demonstrated the transformation 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 cells to acquire oncogene addiction, and that oncogene addiction is not associated with transformation activity.
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影响因子：
--
作者：
Liu Z;Wang L;Yang J;Bandyopadhyay A;Kaklamani V;Wang S;Sun LZ
通讯作者：
Sun LZ
DOI：
10.1073/pnas.0808757105
发表时间：
2008-12-30
影响因子：
11.1
作者：
Di Nicolantonio, Federica;Arena, Sabrina;Bardelli, Alberto
通讯作者：
Bardelli, Alberto
影响因子：
8
作者：
Cheng H;Liu P;Ohlson C;Xu E;Symonds L;Isabella A;Muller WJ;Lin NU;Krop IE;Roberts TM;Winer EP;Arteaga CL;Zhao JJ
通讯作者：
Zhao JJ
影响因子：
64.5
作者：
Moffat, J;Grueneberg, DA;Root, DE
通讯作者：
Root, DE
影响因子：
8
作者：
Karasarides, M;Chiloeches, A;Marais, R
通讯作者：
Marais, R