title: Methylation of RAR-β2, RASSF1A, and CDKN2A genes induced by nickel subsulfide and nickel-carcinogenesis in rats.
abstract: OBJECTIVE
  To investigate the expression variation of RAR-β2, RASSF1A, and CDKN2A gene in the process of nickel-induced carcinogenesis.
  
  
  METHODS
  Nickel subsulfide (Ni(3)S(2)) at dose of 10 mg was given to Wistar rats by intramuscular injection. The mRNA expression of the three genes in induced tumors and their lung metastasis were examined by Real-time PCR. The methylation status of the 5' region of these genes were detected by Quantitative Real-time methylation specific PCR.
  
  
  RESULTS
  The mRNA expressions of the three genes both in muscle and lung tumor were decreased distinctly in comparison with normal tissue. But hypermethylation was found only in muscle tumor.
  
  
  CONCLUSIONS
  These findings suggest that loss of function or decrease of RAR-β2, RASSF1A, and CDKN2A, as well as the hypermethylation of 5' region of these genes, are related with nickel exposure.
authors.affiliation: Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200092, China. junzhang@tongji.edu.cn
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: MengJie
authors.initials: M
authors.lastname: Li
authors.forename: YouJun
authors.initials: Y
authors.lastname: Wu
authors.forename: YingYing
authors.initials: Y
authors.lastname: Fan
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: LiLi
authors.initials: L
authors.lastname: Tan
authors.forename: ZhiHua
authors.initials: Z
authors.lastname: Shao
authors.forename: HongJun
authors.initials: H
authors.lastname: Shi
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D019042:Muscle Neoplasms / Q000139:chemically induced / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D019941:Cyclin-Dependent Kinase Inhibitor p16; C560857:RASSF1 protein, rat; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta; D009532:Nickel; C017557:nickel subsulfide