DECs属于bHLH类转录因子，包括DEC1和DEC2两种蛋白，调控生物钟基因的表达，也参与细胞周期的调节。DEC1还可诱导肿瘤细胞衰老，抑制细胞增殖。有研究表明，生物钟基因Bmal1、Per、Clock的表达异常，可引起细胞衰老，从而抑制细胞增殖。此外，在衰老的人乳腺癌细胞中发现，衰老相关因子ETS1、MAP2K3的含量显著增加。这些研究提示，作为转录因子，DEC1、DEC2可能通过调控生物钟基因的表达，或者调节衰老相关因子的含量来调控肿瘤细胞衰老，从而抑制肿瘤细胞的增殖。 我们在前期工作中已克隆了人DEC1和DEC2基因，拟在人乳腺癌细胞中研究DEC1和DEC2对乳腺癌细胞衰老的调控作用，并通过研究DEC1和DEC2对生物钟基因的调控及其对ETS1、MAP2K3的表达调控，从而阐明DEC1和DEC2对人乳腺癌细胞衰老的调控机制。本项目的开展将为临床治疗乳腺癌提供更多的理论参考依据。

DECs, basic helix-loop-helix(bHLH) transcription factors including DEC1 and DEC2,are involved in regulation of tumor growth,cell cycle progression and circadian rhythms.Moreover,DEC1 induces senescence in multiple cell types,such as mouse diploid fibroblasts HIT3T3 cells and,human embryonic kidney HEK293 cells and human colorectal carcinoma cells,and suppress cell proliferation. However,the roles of DEC1 and DEC2 expression in senescence of human breast cancer cell are poorly understood.It is shown that abnormal expression of clock genes，such as Bmal1、Per、Clock,induces cellular senescence and restrains cell proliferation.Moreover,it has been reported that distinct increases in senescence-related factors ETS1 and MAP2K3 were observed in senescent human breast cancer cells.These data suggest that DEC1 and DEC2 may regulate tumor cell senescence and suppress cell proliferation,through regulating expression of clock genes or senescence-related factors.Therefore, it is possible that ETS1,MAP2K3 and expression products of clock genes are downstream targets of DEC1 and DEC2 to induce cellular senescence. We have cloned these two genes,human Dec1 and Dec2,and are ready to research their regulation on senescence of human breast cancer cells.Moreover,we want to illustrate their regulation mechanism, through regulating expression of clock genes or senescence-related factors. This project will help us understand the mechanism of DECs mediated cellular senescence, explain the molecular mechanism of breast cancer at the genetic level, and provide theoretical reference on breast cancer treatment.