Identification of large-scale molecular changes of Autotaxin(ENPP2) knock-down by small interfering RNA in breast cancer cells.

Abstract

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.

• Authors: Ji Heon Noh, So Yeon Ryu, Jung Woo Eun, Jaehwi Song, Young Min Ahn, Su Young Kim, Sug Hyung Lee, Won Sang Park, Nam Jin Yoo, Jung Young Lee, Shi Nae Lee, Suk Woo Nam
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 288 Issue 1-2 Pg. 91-106 (Aug 2006) ISSN: 0300-8177 [Print] Netherlands
• PMID: 16601922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Multienzyme Complexes
• RNA, Small Interfering
• Phosphoric Diester Hydrolases
• Phosphodiesterase I
• alkylglycerophosphoethanolamine phosphodiesterase
• Pyrophosphatases

Topics

• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Female
• Humans
• Multienzyme Complexes (antagonists & inhibitors, genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Phosphodiesterase I (antagonists & inhibitors, genetics, metabolism)
• Phosphoric Diester Hydrolases
• Pyrophosphatases (antagonists & inhibitors, genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (pharmacology)
• Time Factors
• Transfection