Gao A C, Lou W, Isaacs J T
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA.
Clin Cancer Res. 2000 Feb;6(2):493-7.
Previous studies demonstrated that the GBX2 homeobox gene is consistently overexpressed in cultured human prostate cancer cell lines. In this study, the human GBX2 cDNA was cloned and a quantitative reverse transcription-PCR method used to demonstrate that GBX2 mRNA expression is enhanced in approximately 70% of human prostate cancer tissues compared with normal human prostate tissues. Purified recombinant GBX2 protein binds specifically to an ATTA motif within the promoter of the interleukin 6 (IL-6) gene. Using an antisense approach, down-regulation of the expression of GBX2 correlated with decreased expression of IL-6 and an inhibition of tumorigenicity of PC3 human prostate cancer cells. In addition, in vitro growth of the antisense clones was partially restored by exogenous addition of recombinant IL-6 protein to the culture media. These data demonstrated that enhanced GBX2 expression results in a stimulation of malignant growth of prostate cancer cells and that part of this stimulation involves up-regulation in the transcription of the IL-6 gene.
先前的研究表明，GBX2同源框基因在培养的人前列腺癌细胞系中持续过度表达。在本研究中，克隆了人GBX2 cDNA，并采用定量逆转录PCR方法证明，与正常人前列腺组织相比，约70%的人前列腺癌组织中GBX2 mRNA表达增强。纯化的重组GBX2蛋白特异性结合白细胞介素6（IL-6）基因启动子内的ATTA基序。采用反义方法，GBX2表达的下调与IL-6表达的降低以及PC3人前列腺癌细胞致瘤性的抑制相关。此外，通过向培养基中外源添加重组IL-6蛋白，反义克隆的体外生长得到部分恢复。这些数据表明，GBX2表达增强导致前列腺癌细胞恶性生长的刺激，并且这种刺激的一部分涉及IL-6基因转录的上调。
