title: Aberrant methylation of p21 gene in lung cancer and malignant pleural mesothelioma.
abstract: Suppression of p21 has been implicated in the genesis and progression of many human malignancies. DNA methylation is an important mechanism of gene silencing in human malignancies. In this study, we examined the expression status and aberrant methylaion of p21 in lung cancers and malignant pleural mesotheliomas (MPM). We used 12 small cell lung cancer (SCLC) cell lines, 13 non-small cell lung cancer (NSCLC) cell lines, 50 primary NSCLCs, 6 MPM cell lines and 10 primary MPMs. The expression and methylation of p21 was examined by reverse transcription-PCR (RT-PCR), Western blotting and methylation-specific PCR (MSP) assay. Loss of p21 protein expression was observed in 7 SCLC cell lines (58.3%), 5 NSCLC cell lines (38.5%) and 3 MPM cell lines (50%) while mRNA expression was lost in 2 SCLC cell lines (16.7%), 2 NSCLC cell lines (15.4%) and none of the MPM cell lines. Aberrant methylation of p21 was found in 8.3% of SCLC cell lines, 30.2% of NSCLCs and 6.3% of MPMs. Among primary NSCLCs, methylation in adenocarcinomas was significantly more frequent than in squamous cell carcinomas. Loss of p21 expression was frequently observed in lung cancers and MPMs and aberrant methylation was one of the mechanisms of suppression of p21, especially in NSCLCs.
authors.affiliation: Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Teramen
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Tanaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ueno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kubo
authors.forename: Midori
authors.initials: M
authors.lastname: Ando
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Asano
authors.forename: Harvery I
authors.initials: HI
authors.lastname: Pass
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Miyoshi
mesh_terms: D000368:Aged; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism*; D010997:Pleural Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger