Circadian gene mPer2 overexpression induces cancer cell apoptosis

Cancer Sci. 2006 Jul;97(7):589-96. doi: 10.1111/j.1349-7006.2006.00225.x.


The Period2 gene, an indispensable component of the circadian clock, not only modulates circadian oscillations, but also regulates organic function. We examined whether overexpression of the mouse Period2 gene (mPer2) in tumor cells influences cell growth and induces apoptosis. Overexpression of PERIOD2 in the mouse Lewis lung carcinoma cell line (LLC) and mammary carcinoma cell line (EMT6) results in reduced cellular proliferation and rapid apoptosis, but not in NIH 3T3 cells. Overexpressed mPER2 also altered the expression of apoptosis-related genes. The mRNA and protein levels of c-Myc, Bcl-X(L) and Bcl-2 were downregulated, whereas the expression of p53 and bax was upregulated in mPER2-overexpressing LLC cells compared with control cells transferred with empty plasmid. Our results suggest that the circadian gene mPeriod2 may play an important role in tumor suppression by inducing apoptotic cell death, which is attributable to enhanced pro-apoptotis signaling and attenuated anti-apoptosis processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Lewis Lung / genetics*
  • Carcinoma, Lewis Lung / ultrastructure
  • Cell Cycle Proteins
  • Cell Proliferation
  • Circadian Rhythm / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor / physiology*
  • Mammary Neoplasms, Animal / genetics*
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Period Circadian Proteins
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation
  • bcl-X Protein / genetics


  • Cell Cycle Proteins
  • Myc protein, mouse
  • Nuclear Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • bcl-X Protein