哺乳动物DMRTs的结构、功能及其与肿瘤的关系

Mammalian DMRTs:Structure,function and relationship with cancer

DMRT基因家族是一个与性别决定有关的基因家族,其编码的转录因子DMRTs蛋白(除DMRT8外)均具有一个DM(double-sex and mab-3)结构域,并通过该结构域与DNA结合而发挥调控作用。目前研究表明,DMRT基因家族在性器官发育(如性别分化、性腺发育、生殖细胞发育等)与性外器官发育(如肌肉软骨发育、神经系统发育等)中均具有重要作用;同时也有学者提出DMRTs可能参与肿瘤(如前列腺癌、乳腺癌、肺癌等)的发生和发展。本文综述了以人与小鼠为主的哺乳动物DMRTs/Dmrts的结构、在性器官发育与性外器官发育中的重要功能及其与肿瘤的关系的研究进展,提示DMRT基因家族在多器官发育及多种肿瘤发生和发展及治疗等过程中可能发挥作用,能够作为深入研究肿瘤发病机制与治疗策略的候选基因。

DMRT,a gene family related to sexual determination,encodes a large group of transcription factors(DMRTs)with the double-sex and mab-3(DM)domain(except for DMRT8),which is able to bind to and regulate DNAs.Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs(such as gender differentiation,gonadal development,germ cell development,etc.)as well as extrasexual organs(such as musculocartilage development,nervous system development,etc.).Additionally,it has been suggested that DMRTs may be involved in the cancer development and progression(such as prostate cancer,breast cancer,lung cancer,etc.).This review summarizes the research progress about the mammalian DMRTs’structure,function and its critical role in cancer development,progression and therapy(mainly in human and mice),which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.