PDCD4 expression inversely correlated with miR-21 levels in gastric cancers.
OBJECTIVE
The specific aim of this study was to investigate whether the PDCD4 gene is involved in the development and progression of gastric cancer.


METHODS
We examined the genetic and epigenetic alterations of the PDCD4 gene as well as the expression of PDCD4 protein in gastric cancers. The mRNA expression of PDCD4 and miRNA-21 expression were also analyzed using quantitative real-time RT-PCR.


RESULTS
Loss or reduced PDCD4 expression was observed in 79 (36.7%) of 215 gastric cancer specimens. Statistically, altered PDCD4 expression was not associated with the clinicopathological parameters, including tumor differentiation, location, lymph node metastasis and overall survival (P > 0.05). miRNA-21 overexpression was frequently detected in gastric cancers (31 of 46, 67.4%), and there was a significant inverse correlation between miRNA-21 and PDCD4 protein expression (P = 0.029), but not between miRNA-21 and PDCD4 mRNA expression. In genetic analysis, no mutation was detected in the coding region of the PDCD4 gene, and promoter hypermethylation was found in 24 (36.4%) of the 66 gastric cancer samples.


CONCLUSIONS
Our data suggest that overexpression of miRNA-21 and reduced or loss of PDCD4 expression may play a role in the development and progression of gastric cancers.
Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
Zhang
Z
Cao
Jung Hwan
JH
Yoon
Suk Woo
SW
Nam
Jung Young
JY
Lee
Won Sang
WS
Park
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D013267:Stilbenes; D000077185:Resveratrol