Gabellini Nadia, Masola Valentina
Department of Biological Chemistry, University of Padova, 35121 Padova, Italy.
Int J Cell Biol. 2009;2009:417197. doi: 10.1155/2009/417197. Epub 2009 Oct 7.
The LGI1 gene was suggested to function as tumor suppressor for its ability to reduce malignant features of glioblastoma cells. In support to this proposal were the findings that overexpression of LGI1 in neuroblastoma cells inhibited proliferation and induced apoptosis. In this study we performed stable LGI1 expression in HeLa cells to examine whether the noxious effect of LGI1 might be extended to cancer cells of diverse origin. HeLa cell clones stably expressing LGI1 exhibited a significant impairment of proliferation and a consistent increase of cell death when compared with control cells lacking expression of LGI1. Expression of LGI1 increased the activity of apoptosis effectors caspase-3/7; furthermore it downregulated the antiapoptotic BCL2 gene and upregulated the proapoptotic BAX gene expression, suggesting that the cause of HeLa cells death might be an increased susceptibility to apoptosis induced by LGI1. The results suggested that LGI1 is capable to restrain growth and survival of adenocarcinoma cells such as HeLa.
LGI1基因因其能够降低胶质母细胞瘤细胞的恶性特征而被认为具有肿瘤抑制功能。支持这一观点的发现是,在神经母细胞瘤细胞中过表达LGI1可抑制增殖并诱导凋亡。在本研究中,我们在HeLa细胞中进行了稳定的LGI1表达,以检查LGI1的有害作用是否可能扩展到不同来源的癌细胞。与缺乏LGI1表达的对照细胞相比,稳定表达LGI1的HeLa细胞克隆表现出显著的增殖受损和细胞死亡持续增加。LGI1的表达增加了凋亡效应因子caspase-3/7的活性;此外,它下调了抗凋亡BCL2基因并上调了促凋亡BAX基因的表达,这表明HeLa细胞死亡的原因可能是对LGI1诱导的凋亡敏感性增加。结果表明,LGI1能够抑制腺癌HeLa细胞的生长和存活。