Wang Ning, Wei Heng, Yin Duo, Lu Yanming, Zhang Yao, Jiang Di, Jiang Yan, Zhang Shulan
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang 110004, People's Republic of China.
Int J Clin Exp Pathol. 2014 Jun 15;7(7):4016-23. eCollection 2014.
Cyclin D1b is one of two proteins translated from cyclin D1 transcripts (isoforms a and b) that are generated due to gene polymorphism. Our previous study has reported low cyclin D1b expression in cervical cancer tissue, with an expression level in moderately or poorly differentiated tissues that was significantly lower than that in well-differentiated tissues. However, the functional role of cyclin D1b in cervical cancer remains to be elucidated. In this study, using a cervical cancer cell line with stable expression of cyclin D1b, we found that upregulation of cyclin D1b initiated cell cycle arrest at the G0/G1 phase and induced apoptosis, thereby inhibiting cell proliferation and colony formation. Furthermore, xenograft transplantation experiments in nude mice demonstrated that cyclin D1b upregulation inhibited cancer growth and induce apoptosis in vivo. In conclusion, the present study indicates anti-tumor effects of cyclin D1b in cervical cancer, suggesting that cyclin D1b may represent a potential therapeutic target for cervical cancer.
细胞周期蛋白D1b是由细胞周期蛋白D1转录本(异构体a和b)翻译而来的两种蛋白质之一,这些转录本是由基因多态性产生的。我们之前的研究报道了宫颈癌组织中细胞周期蛋白D1b表达较低,在中分化或低分化组织中的表达水平显著低于高分化组织。然而,细胞周期蛋白D1b在宫颈癌中的功能作用仍有待阐明。在本研究中,我们使用稳定表达细胞周期蛋白D1b的宫颈癌细胞系,发现细胞周期蛋白D1b的上调引发细胞周期在G0/G1期停滞并诱导凋亡,从而抑制细胞增殖和集落形成。此外,裸鼠异种移植实验表明,细胞周期蛋白D1b的上调在体内抑制肿瘤生长并诱导凋亡。总之,本研究表明细胞周期蛋白D1b在宫颈癌中具有抗肿瘤作用,提示细胞周期蛋白D1b可能是宫颈癌的一个潜在治疗靶点。