Identification of large-scale molecular changes of Autotaxin(ENPP2) knock-down by small interfering RNA in breast cancer cells.
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.
Noh
Ji Heon
JH
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.
Ryu
So Yeon
SY
Eun
Jung Woo
JW
Song
Jaehwi
J
Ahn
Young Min
YM
Kim
Su Young
SY
Lee
Sug Hyung
SH
Park
Won Sang
WS
Yoo
Nam Jin
NJ
Lee
Jung Young
JY
Lee
Shi Nae
SN
Nam
Suk Woo
SW
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D000099189:Lysophospholipase D
D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D034741:RNA, Small Interfering; D000099189:Lysophospholipase D