Aberrant methylation of ADAMTS1 in non-small cell lung cancer.
ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) is an extracellular matrix metalloproteinase with protease activity and antiangiogenic activity. It has been suggested that ADAMTS1 plays an important role in tumor growth and metastasis. In this study, we examined ADAMTS1 expression in non-small cell lung cancer (NSCLC), and we also evaluated whether the loss of ADAMTS1 expression is due to aberrant methylation of the gene. In addition, we examined the relationship between ADAMTS1 methylation and clinicopathologic features in NSCLC patients. ADAMTS1 expression was examined using reverse-transcription polymerase chain reaction (PCR), and the methylation status of the gene was evaluated by methylation-specific PCR in NSCLC cell lines (n=10) and primary NSCLC tumors (n=98). Down-regulation of ADAMTS1 was observed in 30% (3/10) of the NSCLC cell lines, and this down-regulation was found to be concordant with aberrant methylation of the gene. Furthermore, ADAMTS1 expression was restored after treatment with the demethylating agent, 5-Aza-2'-deoxycytidine, in cell lines that lacked ADAMTS1 expression. Aberrant methylation of the gene was observed in 31.6% (31 of 98) of the NSCLC tumors, while it was found in only 7.1% (7/98) of the corresponding nonmalignant tissues. Methylation in NSCLC tumors was not correlated with the clinicopathologic features of the patients, such as age, gender, and histology and pathologic staging of the tumor. Taken together, these results suggest that aberrant methylation of ADAMTS1 frequently occurs in NSCLCs and that it may play a role in the pathogenesis of NSCLC.
Choi
Jin Eun
JE
Department of Biochemistry, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu, 700-422, South Korea.
Kim
Dong Sun
DS
Kim
Eun Jin
EJ
Chae
Myung Hwa
MH
Cha
Sung Ick
SI
Kim
Chang Ho
CH
Jheon
Sanghoon
S
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D051722:ADAM Proteins / Q000235:genetics* / Q000378:metabolism; D000071097:ADAMTS1 Protein; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000077209:Decitabine; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D001374:Azacitidine