Tumor Biology

, Volume 34, Issue 2, pp 811–819 | Cite as

Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors

  • Zsuzsanna Lengyel
  • Csenge Lovig
  • Siri Kommedal
  • Rita Keszthelyi
  • György Szekeres
  • Zita Battyáni
  • Valér Csernus
  • András Dávid Nagy
Research Article
First Online:
Received:
Accepted:

Abstract

The majority of our genes may be regulated in a daily rhythm, including the genes for cell cycle control. Epidemiological and genetic evidences suggest that disruption of circadian timing mechanisms makes our cells more vulnerable to cancer formation. The aim of this study was to investigate the relationship between expression patterns of circadian clock genes (period homolog (per)1, per2, clock, and cry1) and tumor development by analyzing human skin biopsies of malignant melanoma and nonmalignant naevus tumors. We found that mRNA levels and nuclear immunopositivity for the investigated clock genes were reduced by 30–60 % in both melanoma and in naevus biopsies if compared with adjacent nontumorous samples. The alterations in melanoma presented significant associations with clinicopathological characteristics (e.g., Breslow thickness). Contrary to previous reports, the moderate decrease of per1 expression seen in malignant tissues could not be linked to malignant transformation itself; rather, it reflects only the alterations in tissue composition. In turn, clock expression was upregulated in nontumorous cells of melanoma biopsies but not in melanoma cells or naevus cells. As this gene (clock) is closely related to cellular metabolism, our data suggest its role in the impaired regulation of metabolism in malignant tumors. Our results present the first clinical evidence for a possible link between circadian clock genes and human skin tumorigenesis.

Keywords

Clock genes Melanoma Naevus Circadian rhythm Human skin cancer 
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Notes

Acknowledgments

Routine histopathological classification of the human tumor biopsies was done by Dr. Endre Kálmán (University of Pécs). We thank Dr. Janos Posfai (New England Biolabs Inc.) and Dr. Balazs Gaszner (University of Pécs) for the helpful remarks on the text. This work was supported by the Hungarian Medical Research Council (ETT50072-1133-99), the Hungarian National Science Fund (OTKA PD100927), and the University of Pécs (ÁOK KA34039-10-18).

Conflict of interest

None

Supplementary material

13277_2012_611_MOESM1_ESM.tif (4.2 mb)
Suppl. Fig. 1 Representative microphotographs of CLOCK immunohistochemistry on human skin biopsies. Top, melanoma malignum; bottom, naevus. Left column, tumorous area; right column, adjacent nontumorous area. Arrows show examples for cells with strong nuclear immunopositivity. Empty arrowheads show examples for cells considered as negative for nuclear immunostaining (TIFF 4278 kb)
13277_2012_611_MOESM2_ESM.tif (5.6 mb)
Suppl. Fig. 2 Representative microphotographs of PER1 immunohistochemistry on human skin biopsies. Top, melanoma malignum; bottom, naevus. Left column, tumorous area; right column, adjacent nontumorous area. Arrows show examples for cells with strong nuclear immunopositivity. Empty arrowheads show examples for cells considered as negative for nuclear immunostaining (TIFF 5772 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Zsuzsanna Lengyel
    • 1
  • Csenge Lovig
    • 1
  • Siri Kommedal
    • 2
  • Rita Keszthelyi
    • 3
  • György Szekeres
    • 3
  • Zita Battyáni
    • 1
  • Valér Csernus
    • 2
  • András Dávid Nagy
    • 2
  1. 1.Department of Dermatology, Medical SchoolUniversity of PécsPécsHungary
  2. 2.Department of Anatomy, Medical SchoolUniversity of PécsPécsHungary
  3. 3.Histopathology Ltd, PécsPécsHungary

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