title: Correlation between deregulated expression of PER2 gene and degree of glioma malignancy.
abstract: OBJECTIVE
  Growing evidence indicates that disruption of circadian rhythms may be a risk factor for the development of glioma. However, the molecular mechanisms underlying the genetic regulation of circadian rhythms in glioma cells have yet to be explored.
  
  
  METHODS
  Using immunohistochemical staining and methylation-specific PCR techniques, we examined the expression of the period 2 (PER2) gene, one of the most important clock genes, epidermal growth factor receptor (EGFR), and proliferating cell nuclear antigen (PCNA) in 92 gliomas.
  
  
  RESULTS
  Our results revealed disturbances in the expression of PER2 in most (52.17%) glioma cells compared with the expression in nearby noncancerous cells, and indicated that PER2 gene deregulation most likely occurs via methylation of PER2 promoters. The protein expression of PCNA and EGFR was significantly higher in high-grade than low-grade gliomas (P < 0.05). Furthermore, a negative correlation was detected between the protein expression of PER2 and PCNA and EGFR in glioma.
  
  
  CONCLUSIONS
  Because the circadian clock regulates the expression of cell cycle-related genes, we suggest that disturbances in PER2 gene expression may disrupt the regulation of the circadian clock, thus enhancing the survival of cancer cells and promoting carcinogenesis.
authors: Fan
authors: F
authors: Wang
authors: Yong
authors: Y
authors: Luo
authors: Caiyan
authors: C
authors: Li
authors: Lvan
authors: L
authors: Chen
mesh_terms: D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D063646:Carcinogenesis; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D018773:Genes, erbB-1; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000378:metabolism / Q000473:pathology; D056950:Period Circadian Proteins / Q000032:analysis / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000378:metabolism*; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D018809:Proliferating Cell Nuclear Antigen; C512478:EGFR protein, human; D066246:ErbB Receptors