Abnormal Expression of Period 1 (PER1) in Endometrial Carcinoma

J Pathol. 2005 May;206(1):111-20. doi: 10.1002/path.1756.

Abstract

The development of endometrial carcinoma (EC) is a multiple-step process, which includes inactivation of tumour suppressor genes, activation of oncogenes, and disturbance of cancer-related genes. Recent studies have shown that the circadian cycle may influence cancer development and prognosis. In this study, the expression of a circadian gene, PER1, was examined in 35 ECs and paired non-tumour tissues by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Expression levels of PER1 were significantly decreased in EC, and mutational analysis of the coding regions, together with methylation analysis of cytosine-phosphate guanosine (CpG) sites in the promoter area, was performed to investigate the possible mechanisms. The analyses detected four single nucleotide polymorphisms in both tumour and non-tumour tissues, which had no relationship with the expression of PER1. In the promoter area of the PER1 gene, the CpG sites were methylated in 31.4% of ECs, but in 11.4% of paired non-tumour tissues (p < 0.05). These results suggest that the down-regulation of PER1 expression in EC was partly due to inactivation of the PER1 gene by DNA methylation of the promoter and partly due to other factors. Analysis of the relationships between the expression of PER1, P53, c-MYC, cyclin A, cyclin B, and cyclin D1 showed no definite relationship. These results suggest that down-regulation of the PER1 gene disrupts the circadian rhythm, which may favour the survival of endometrial cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma / genetics*
  • Case-Control Studies
  • Cell Cycle Proteins
  • Circadian Rhythm*
  • Cyclin A / analysis
  • Cyclin B / analysis
  • Cyclin D1 / analysis
  • DNA Methylation
  • DNA Mutational Analysis
  • Endometrial Neoplasms / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry / methods
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Period Circadian Proteins
  • Prognosis
  • Promoter Regions, Genetic*
  • Proto-Oncogene Proteins c-myc / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / analysis

Substances

  • Cell Cycle Proteins
  • Cyclin A
  • Cyclin B
  • Nuclear Proteins
  • PER1 protein, human
  • Period Circadian Proteins
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • Cyclin D1