Simons Johannes W I M
Department of Toxicogenetics, MGC, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Biol Direct. 2006 Apr 2;1:9. doi: 10.1186/1745-6150-1-9.
Microscopic examination of living cells often reveals that cells from some cell strains appear to be in a permanent state of disarray without obvious reason. In all probability such a disorderly state affects cell functioning. The aim of this study was to establish whether a disorderly state could occur that adversely affects gene expression profiles and whether such a state might have biomedical consequences. To this end, the expression profiles of the 14 genes of the proteasome derived from the GEO SAGE database were utilized as a model system.
By adopting the overall expression profile as the standard for normal expression, deviation in transcription was frequently observed. Each deviating tissue exhibited its own characteristic profile of over-expressed and under-expressed genes. Moreover such a specific deviating profile appeared to be epigenetic in origin and could be stably transmitted to a clonal derivative e.g. from a precancerous normal tissue to its tumor. A significantly greater degree of deviation was observed in the expression profiles from the tumor tissues. The changes in the expression of different genes display a network of interdependencies. Therefore our hypothesis is that deviating profiles reflect disorder in the localization of genes within the nucleus. The underlying cause(s) for these disorderly states remain obscure; it could be noise and/or deterministic chaos. Presence of mutational damage does not appear to be predominantly involved.
As disturbances in expression profiles frequently occur and have biomedical consequences, its determination could prove of value in several fields of biomedical research.
对活细胞进行显微镜检查常常发现,某些细胞系的细胞似乎毫无明显原因地处于一种永久的紊乱状态。很有可能这种无序状态会影响细胞功能。本研究的目的是确定是否会出现一种对基因表达谱产生不利影响的无序状态,以及这种状态是否可能具有生物医学后果。为此,将来自GEO SAGE数据库的蛋白酶体14个基因的表达谱用作模型系统。
以整体表达谱作为正常表达的标准,经常观察到转录偏差。每个偏差组织都表现出其自身过表达和低表达基因的特征性谱。此外,这种特定的偏差谱似乎起源于表观遗传,并且可以稳定地传递给克隆衍生物,例如从癌前正常组织传递到其肿瘤。在肿瘤组织的表达谱中观察到明显更大程度的偏差。不同基因表达的变化显示出相互依赖的网络。因此,我们的假设是偏差谱反映了基因在细胞核内定位的紊乱。这些无序状态的潜在原因仍然不清楚;可能是噪声和/或确定性混沌。突变损伤似乎并非主要因素。
由于表达谱的干扰经常发生并具有生物医学后果,其测定在生物医学研究的几个领域可能具有价值。