Noh Ji Heon, Ryu So Yeon, Eun Jung Woo, Song Jaehwi, Ahn Young Min, Kim Su Young, Lee Sug Hyung, Park Won Sang, Yoo Nam Jin, Lee Jung Young, Lee Shi Nae, Nam Suk Woo
Department of Pathology, College of Medicine and Microdissection Genomics Research Center, The Catholic University of Korea, Banpo-dong #505, Seocho-gu, Seoul, 137-701, Korea.
Mol Cell Biochem. 2006 Aug;288(1-2):91-106. doi: 10.1007/s11010-006-9124-8. Epub 2006 Apr 7.
To understand comprehensive molecular mechanisms by which Autotaxin (ENPP2) mediates, we identified large-scale molecular changes responsible for aberrant expression of Autotaxin (ATX) on breast cancer cells by using DNA microarrays. Transcriptional over-expression of ENPP2 gene was endogenously silenced by using RNA interference technique, and then recapitulated corresponding molecular changes in MDA435 breast cancer cells. Application of nonparametric Wilcoxon statistical analyses (P<0.05) and the selection criteria of 2-fold differential gene expression change resulted in the identification of 368 genes including 133 up-regulated and 235 genes under-expressed in ENPP2-silencing MDA435 cells. Most of the functional categories of identified genes are associated with cellular metabolism, cytoskeleton organization, transcription regulation, signal transduction as well as cellular organization and biogenesis. Our data suggest that the molecular signature identified by the ENPP2-silencing methods may represent potential candidates that can explain the complicated characteristics of ATX and may serve as biomarkers, for the development of molecular-targeting therapy, in human breast cancer.
为了解自分泌运动因子（ENPP2）介导的全面分子机制，我们通过DNA微阵列鉴定了导致乳腺癌细胞中自分泌运动因子（ATX）异常表达的大规模分子变化。利用RNA干扰技术内源性沉默ENPP2基因的转录过表达，然后在MDA435乳腺癌细胞中重现相应的分子变化。应用非参数Wilcoxon统计分析（P<0.05）和2倍差异基因表达变化的选择标准，在ENPP2沉默的MDA435细胞中鉴定出368个基因，其中包括133个上调基因和235个下调基因。鉴定出的基因的大多数功能类别与细胞代谢、细胞骨架组织、转录调控、信号转导以及细胞组织和生物发生有关。我们的数据表明，通过ENPP2沉默方法鉴定的分子特征可能代表了解释ATX复杂特征的潜在候选物，并且可能作为生物标志物，用于人类乳腺癌分子靶向治疗的开发。
