Significance of methylation status and the expression of RECK mRNA in lung tissue of patients with NSCLC.
OBJECTIVE
RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is a glycoprotein which negatively regulates the activity of matrix metalloproteinases (MMPs). We analyzed differences in RECK mRNA expression in histological types of non-small cell lung cancer (NSCLC) and the relationship between promoter methylation status of RECK gene, level of RECK mRNA expression and clinicopathological values of patients with NSCLC.


METHODS
Methylation status of the promoter and the expression of RECK mRNA were analyzed in paired tissue samples (tumor and control) of 50 patients with NSCLC. The methylation status of the RECK promoter was assessed using methylation-specific PCR. The level of RECK mRNA expression was measured using an RT real-time PCR method.


RESULTS
Lower expression of RECK mRNA in NSCLC tissue was recorded compared to normal tissue (p=0.0032). Significantly lower expression of RECK in squamous cell carcinoma (SCC) tissue was observed in comparison with adenocarcinoma tissue (p=0.0051). Significant differences in expression of RECK in stages IB-IIIA were found in comparison with stage IA (p=0.0455). There was a significantly lower expression of RECK mRNA in NSCLC tissue in samples with positive RECK promoter methylation status in comparison with samples with negative promoter methylation status (p=0.0400).


CONCLUSIONS
We showed that there were differences in expression between histological types of NSCLC (SCC, adenocarcinoma). There was a higher expression of RECK in stage IA in comparison with stages IB-IIIA. Our results indicate that RECK could be classified as a tumor suppressor gene and is an interesting target for further investigation of MMP inhibitors.
Pesta
M
M
Department of Oncology and Radiotherapy, E.Benese 13, 305 99 Pilsen, Czech Republic.
Kulda
V
V
Topolcan
O
O
Safranek
J
J
Vrzalova
J
J
Cerny
R
R
Holubec
L
L
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D058851:GPI-Linked Proteins; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D012333:RNA, Messenger