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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-4-5
pubmed:abstractText
Aberrant methylation of promoter CpG that causes silencing of tumor suppressor genes (TSGs) may play a key role in the carcinogenesis of many cancer types. RASSF1A, regarded as a TSG, has been extensively studied in lung cancer and other malignant tumors, whereas RASGRF2 has only been reported to possibly play a role in the pathogenesis of pancreatic cancer cell lines. The aims of our study were to i) determine the methylation profile of RASGRF2 and ii) compare the methylation profiles of RASGRF2 with RASSF1A in lung cancer. We examined RASGRF2 expression by reverse transcription PCR and aberrant methylation of RASGRF2 by methylation-specific PCR in lung cancer cell lines. Loss of RASGRF2 expression was presented in 36% lung cancer cell lines while aberrant methylation of RASGRF2 was present in 30% (3/10) non-small cell lung cancer (NSCLC) cell lines and in 25% (1/4) small cell lung cancer (SCLC) cell lines. The concordance between loss of expression and aberrant methylation of RASGRF2 was 86% (12/14). RASGRF2 expression was restored after treatment with the demethylating agent, 5-aza-2'-deoxycytidine in all four cell lines tested that downregulated RASGRF2 expression. Among primary NSCLC, RASGRF2 and RASSF1A methylation was observed in 34% (39/114) and 39% (44/114) of cases respectively, while it was observed in only 7% (4/57) and none of the corresponding non-malignant lung tissue. There is no correlation between RASGRF2 and RASSF1A methylation status. Both RASGRF2 and RASSF1A methylation did not associate with clinical characteristics. Frequent methylation and silencing of RASGRF2 in tumor cells may play an important role, different from that of RASSF1A, in the carcinogenesis of NSCLC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1281-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16596198-Aged, pubmed-meshheading:16596198-Azacitidine, pubmed-meshheading:16596198-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:16596198-Cells, Cultured, pubmed-meshheading:16596198-DNA Methylation, pubmed-meshheading:16596198-Enzyme Inhibitors, pubmed-meshheading:16596198-Female, pubmed-meshheading:16596198-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16596198-Gene Silencing, pubmed-meshheading:16596198-Humans, pubmed-meshheading:16596198-Lung, pubmed-meshheading:16596198-Lung Neoplasms, pubmed-meshheading:16596198-Male, pubmed-meshheading:16596198-Neoplasm Staging, pubmed-meshheading:16596198-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16596198-Tumor Suppressor Proteins, pubmed-meshheading:16596198-ras Guanine Nucleotide Exchange Factors
pubmed:year
2006
pubmed:articleTitle
Aberrant methylation of RASGRF2 and RASSF1A in human non-small cell lung cancer.
pubmed:affiliation
Division of Thoracic Diseases, Chiba Cancer Center, Nitona, Chiba 260-8717, PR China.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't