title: Hypermethylation of growth arrest DNA-damage-inducible gene 45 in non-small cell lung cancer and its relationship with clinicopathologic features.
abstract: The growth arrest DNA-damage-inducible protein 45 (GADD45) can serve as a key coordinator of the stress response by regulating cell cycle progression, genomic stability, DNA repair, and other stress-related responses. Although deregulation of GADD45 expression has been reported in several types of human tumors, its role in lung cancer is still unknown. DNA hypermethylation of promoter CpG islands is known to be a major mechanism for epigenetic inactivation of tumor suppressor genes. We investigated the methylation status of GADD45 family genes (GADD45A, B, and G) in 139 patients with non-small cell lung cancer (NSCLC) using methylation-specific PCR (MSP) and correlated the results with clinicopathologic features of the patients. Methylation frequencies in tumors were 1.4% for GADD45A, 7.2% for GADD45B, and 31.6% for GADD45G. RT-PCR and MSP analysis showed that promoter methylation of the GADD45G gene resulted in downregulation of its mRNA expression. GADD45G methylation was significantly more frequent in female patients than male patients (P = 0.035). This finding suggests that methylation-associated down-regulation of the GADD45G gene may be involved in lung tumorigenesis.
authors.affiliation: Department of Anatomy, School of Medicine, Kyungpook National University, Daegu 702-422, Korea.
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Na
authors.forename: Su Man
authors.initials: SM
authors.lastname: Lee
authors.forename: Hae Sook
authors.initials: HS
authors.lastname: Hong
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097642:GADD45 Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C485654:GADD45G protein, human; D000097642:GADD45 Proteins