EGR1促进前列腺增生上皮细胞系BPH-1的增殖

EGR1 Promotes Proliferation in Prostatic Hyperplasia Epithelial BPH-1 Cells

早期生长反应基因1(early growth response gene 1,EGR1)属于锌指结构的转录因子,表达受多种因素调节,其蛋白至少参与对30种以上靶基因的调控.EGR1在前列腺癌中作为癌基因其表达量与肿瘤的恶性程度成正比,而在良性前列腺增生(benign prostatic hyperplasia,BPH)中其机制和功能尚不明确.EGR1在大鼠和人BPH组织中表达升高,提示EGR1在BPH进程中发挥重要作用.通过构建EGR1表达载体,以及EGR1稳定转染的良性前列腺增生上皮细胞系BPH-1,可见过表达EGR1的BPH-1细胞增殖能力升高.通过转染siRNA将EGR1表达抑制,BPH-1细胞的增殖水平下降.雌激素在BPH疾病进程中发挥重要作用,在BPH-1细胞中,雌二醇(estradiol,E2)能促进EGR1的核迁移,从而激活其转录活性.在EGR1稳定转染的BPH-1细胞系中胰岛素样生长因子2(insulin-like growth factor 2,IGF2)的表达上调,表明EGR1可以调控IGF2的表达.同时发现,E2可上调BPH-1细胞中IGF2的表达,而将EGR1敲除后上调效果消失,说明E2通过EGR1来调节IGF2的表达.E2对EGR1及其靶基因的调节可能是E2参与影响BPH的重要环节.本文为进一步研究E2和EGR1在BPH中作用奠定了基础.

Early growth response gene 1 （EGR1） is a member of a zinc-finger transcription factor family.EGR1 can be induced by several factors and it regulates more than 30 target genes. As an oncogene, EGR1 expression increases with the degree of malignancy in prostate cancer. Compared to the numerous studies of EGR1 in prostate cancer, the research in benign prostatic hyperplasia （BPH） is not enough while the associated mechanisms and functions are still unclear. In this study, we found that EGR1 was highly expressed in both rat and human BPH tissues. EGR1 plays important roles in the BPH progression. We constructed the EGR1 expression vector and the EGR1 stably transfected BPH-1 cell lines. The cell proliferation was promoted by over-expressed EGR1. Furthermore, EGR1 siRNA inhibited BPH-1 cell proliferation. Estrogen plays important roles in BPH progression. In BPH-1 cell lines, estradiol （E2） promoted EGR1 protein nuclear transfer which activated EGRI＇s transcriptional activity. Insulin-like growth factor 2 （IGF2） was up-regulated in EGR1 stably transfected BPH-1 cell lines.Meanwhile, E2 promoted IGF2 expression and the up-regulation could be abolished by knocking down EGR1 which means E2 up-regulates IGF2 via EGR1. The regulation of EGR1 and its target gene may be critical for E2 to exert its influence on BPH progression. This study adds new insights into the function of E2 and EGR1 in BPH.