Chinnappan Dharmaraj, Xiao Dongmei, Ratnasari Anita, Andry Chris, King Thomas C, Weber H Christian
Section of Gastroenterology, Boston University School of Medicine, Boston, MA 02118-2518, USA.
Int J Oncol. 2009 May;34(5):1417-23.
Over-expression of the multifunctional zinc-finger transcription factor Yin Yang 1 (YY1) has been associated with cellular proliferation and resistance to apoptotic stimuli. In this study, we report that YY1 was uniformly highly over-expressed in a wide range of human cancer cell lines and in human colon cancer tissue samples. The examination of YY1-specific mRNA expression demonstrated at least six mRNA isoforms ubiquitously expressed in normal human adult and fetal tissues. Substantial over-expression of two specific mRNA isoforms of 7.5 and 2.9 kb size, respectively, was detected in gastrointestinal and other cancer cells in vitro, whereby mRNA stability differed significantly between various cell lines. YY1 protein expression levels were similar in different colon cancer cell lines. Using FISH analysis of several colorectal cancer cell lines, the human YY1 locus was expectedly identified on chromosome 14q32 and no evidence of gene amplification and chromosomal translocation was observed. However, varying degree of aneuploidy was noted in vitro. YY1 immunoreactivity in human colon tumor samples was found more intense in poorly differentiated tumors than in moderately and well differentiated colon cancers and lower expression levels tended to be associated with shorter survival. In conclusion, YY1 was over-expressed in colon cancer in the absence of gene amplification and chromosomal translocation. YY1 mRNA and protein stability are important regulatory mechanisms of YY1 expression in colon cancer.
多功能锌指转录因子阴阳1(YY1)的过表达与细胞增殖及对凋亡刺激的抗性相关。在本研究中,我们报告YY1在多种人类癌细胞系及人类结肠癌组织样本中均呈一致的高度过表达。对YY1特异性mRNA表达的检测表明,至少有六种mRNA异构体在正常成人及胎儿组织中普遍表达。在体外的胃肠道及其他癌细胞中分别检测到两种大小为7.5 kb和2.9 kb的特异性mRNA异构体大量过表达,不同细胞系间mRNA稳定性存在显著差异。不同结肠癌细胞系中YY1蛋白表达水平相似。通过对几种结肠癌细胞系进行荧光原位杂交分析,预期在14q32染色体上鉴定出人类YY1基因座,未观察到基因扩增及染色体易位的证据。然而,在体外观察到不同程度的非整倍体现象。在人类结肠肿瘤样本中,YY1免疫反应性在低分化肿瘤中比中分化和高分化结肠癌中更强,较低的表达水平往往与较短的生存期相关。总之,在无基因扩增及染色体易位的情况下,YY1在结肠癌中过表达。YY1 mRNA和蛋白稳定性是结肠癌中YY1表达的重要调控机制。