CENP-50 is required for papilloma development in the two-stage skin carcinogenesis model

Cancer Sci. 2020 Aug;111(8):2850-2860. doi: 10.1111/cas.14533. Epub 2020 Jul 6.

Abstract

CENP-50/U is a component of the CENP-O complex (CENP-O/P/Q/R/U) and localizes to the centromere throughout the cell cycle. Aberrant expression of CENP-50/U has been reported in many types of cancers. However, as Cenp-50/U-deficient mice die during early embryogenesis, its functions remain poorly understood in vivo. To investigate the role of Cenp-50/U in skin carcinogenesis, we generated Cenp-50/U conditional knockout (K14CreER -Cenp-50/Ufl/fl ) mice and subjected them to the 7,12-dimethylbenz(a)anthracene (DMBA)/terephthalic acid (TPA) chemical carcinogenesis protocol. As a result, early-stage papillomas decreased in Cenp-50/U-deficient mice. In contrast, Cenp-50/U-deficient mice demonstrated almost the same carcinoma incidence as control mice. Furthermore, mRNA expression analysis using DMBA/TPA-induced papillomas and carcinomas revealed that Cenp-50/U expression levels in papillomas were significantly higher than in carcinomas. These results suggest that Cenp-50/U functions mainly in early papilloma development and it has little effect on malignant conversion.

Keywords: CENP; malignant conversion; mouse models; papilloma; two-stage skin carcinogenesis.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Carcinogenesis / chemically induced
  • Carcinogenesis / pathology*
  • Carcinogens / toxicity
  • Cell Cycle Proteins / deficiency*
  • Cell Cycle Proteins / genetics
  • Humans
  • Mice
  • Mice, Knockout
  • Neoplasms, Experimental / chemically induced
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / pathology*
  • Papilloma / chemically induced
  • Papilloma / genetics
  • Papilloma / pathology*
  • Phthalic Acids / toxicity
  • Skin / drug effects
  • Skin / pathology
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology*

Substances

  • Carcinogens
  • Cell Cycle Proteins
  • MLF1-IP protein, mouse
  • Phthalic Acids
  • 9,10-Dimethyl-1,2-benzanthracene
  • terephthalic acid