Kent Matthew R, Jay Amanda N, Kendall Genevieve C
bioRxiv. 2024 Feb 27:2024.02.23.581802. doi: 10.1101/2024.02.23.581802.
The study of cooperating genes in cancer can lead to mechanistic understanding and identifying potential therapeutic targets. To facilitate these types of studies, we developed a new dual-inducible system utilizing the tetracycline- and cumate-inducible systems driving HES3 and the PAX3::FOXO1 fusion-oncogene, respectively, as cooperating genes from fusion-positive rhabdomyosarcoma. With this new model, we can independently induce expression of either HES3 or PAX3::FOXO1, as well as simultaneously induce expression of both genes. This new model will allow us to further investigate the cooperation between HES3 and PAX3::FOXO1 including the temporal requirements for genetic cooperation. This dual-inducible model can be adapted for any cooperating genes, allowing for independent, simultaneous, or temporally controlled gene expression.
对癌症中协同作用基因的研究有助于深入理解其机制并确定潜在的治疗靶点。为推动此类研究，我们开发了一种新型双诱导系统，该系统利用四环素诱导系统和cumate诱导系统，分别驱动HES3以及PAX3::FOXO1融合癌基因，这两个基因作为融合阳性横纹肌肉瘤中的协同作用基因。借助这个新模型，我们能够独立诱导HES3或PAX3::FOXO1的表达，也能同时诱导这两个基因的表达。这个新模型将使我们能够进一步研究HES3与PAX3::FOXO1之间的协同作用，包括基因协同作用的时间要求。这种双诱导模型可适用于任何协同作用基因，实现独立、同时或时间控制的基因表达。
