范卡
范科尼贫血
癌症
癌症研究
FANCD2
医学
贫血
病理
生物
内科学
基因
DNA修复
遗传学
作者
Ricardo Errazquin,Angustias Page,Anna Suñol,Carmen Segrelles,Estela Carrasco,Jorge Peral,Alicia Garrido-Aranda,Sonia Del Marro,Jessica Ortiz,Corina Lorz,Jordi Minguillón,Jordi Surralles,Cristina Belendez,Martina Alvarez,Judith Balmaña,Ana Bravo,Angel Ramirez,Ramón García-Escudero
标识
DOI:10.1016/j.oraloncology.2022.106184
摘要
Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxicity or multiple recurrences. Translational research on new chemopreventive agents and therapeutic strategies has been unsuccessful partly due to scarcity of disease models or failure to fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca-/-) frequently display pre-malignant lesions in the oral cavity. Moreover, when these animals were crossed with animals having conditional deletion of Trp53 gene in oral mucosa (K14cre;Trp53F2-10/F2-10), they spontaneously developed OSCC with high penetrance and a median latency of less than ten months. Tumors were well differentiated and expressed markers of squamous differentiation, such as keratins K5 and K10. In conclusion, Fanca and Trp53 genes cooperate to suppress oral cancer in mice, and Fanca-/-;K14cre;Trp53F2-10/F2-10 mice constitute the first animal model of spontaneous OSCC in FA.
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