Net1 and Myeov: computationally identified mediators of gastric cancer.
Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.
Leyden
J
J
Gastrointestinal Unit, Mater Misericordiae University Hospital, University College Dublin, Ireland.
Murray
D
D
Moss
A
A
Arumuguma
M
M
Doyle
E
E
McEntee
G
G
O'Keane
C
C
Doran
P
P
MacMathuna
P
P
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
C407245:MYEOV protein, human; C099763:NET1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering