Altered circadian genes expression in breast cancer tissue according to the clinical characteristics

PLoS One. 2018 Jun 29;13(6):e0199622. doi: 10.1371/journal.pone.0199622. eCollection 2018.

Abstract

Breast cancer has a multifactorial etiology. One of the supposed and novel mechanisms is an alteration of circadian gene expression. Circadian genes play a crucial role in many physiological processes. These processes, such as genomic stability, DNA repair mechanism and apoptosis, are frequently disrupted in breast tumors. To assess the significance of circadian gene expression in breast cancer, we carried out an analysis of CLOCK, BMAL1, NPAS2, PER1, PER2, PER3 and CRY1, CRY2, TIMELESS, CSNK1E expression by the use of the quantitative Real-Time PCR technique in tumor tissue and non-tumor adjacent normal tissue sampled from 107 women with a newly diagnosed disease. The obtained data were compared to the clinical and histopathological features. PER1, PER2, PER3, CRY2 were found to be significantly down-expressed, while CLOCK, TIMELESS were over-expressed in the studied tumor samples compared to the non-tumor samples. Only gene expression of CRY1 was significantly down-regulated with progression according to the TNM classification. We found significantly decreased expression of CRY2, PER1, PER2 genes in the ER/PR negative breast tumors compared to the ER/PR positive tumors. Additionally, expression of CRY2, NPAS2 genes had a decreased level in the poorly differentiated tumors in comparison with the well and moderately differentiated ones. Our results indicate that circadian gene expression is altered in breast cancer tissue, which confirms previous observations from various animal and in vitro studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / metabolism*
  • Carcinoma / diagnosis
  • Carcinoma / metabolism
  • Circadian Clocks / physiology
  • Circadian Rhythm Signaling Peptides and Proteins / metabolism*
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging

Substances

  • Circadian Rhythm Signaling Peptides and Proteins

Grant support

This work was supported by the National Science Center (Grant No. 2014/15/N/NZ5/01671) (to ML), https://www.ncn.gov.pl/?language=en, and partially supported by Ministry of Science and Higher Education Poland DIR/WK/2017/01 (to LK), http://www.nauka.gov.pl/en/, and Internal grant for statutory activity at Nofer Institute of Occupational Medicine IMP 14.4/2018. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.