c-Rel is a cell cycle modulator in human melanoma cells

Exp Dermatol. 2019 Feb;28(2):121-128. doi: 10.1111/exd.13848. Epub 2018 Dec 21.

Abstract

Melanoma progression and resistance to therapy are associated with faulty regulation of signalling molecules including the central transcription factor NF-κB. Increased expression of the c-Rel subunit of NF-κB has been described in progressing melanoma, though mechanistic implications of this upregulation remain unclear. To elucidate the functional role of c-Rel in melanoma biology, we have assessed its expression in human melanoma as well as in melanoma cell lines. Suppression of c-Rel expression in four melanoma cell lines resulted in reduced growth and altered cell cycle regulation, namely G2/M and polyploid phase induction. Moreover, mitotic spindle morphology was profoundly altered in three of the cell lines with a predominance of monopolar structures. These findings suggest that c-Rel is involved in G2/M phase regulation, prevention of polyploidy and, consequently, chromosomal stability. Our results highlight a novel tumor-promoting function of c-Rel in human melanoma cells through governing cell cycle regulation.

Keywords: NF-κB; c-Rel; cell cycle; melanoma; mitotic spindle.

MeSH terms

  • Cell Cycle Checkpoints
  • Cell Cycle*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Separation
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Flow Cytometry
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melanoma / metabolism*
  • Proto-Oncogene Proteins c-rel / metabolism*
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Spindle Apparatus
  • Transfection

Substances

  • HIVEN86A protein, human
  • Proto-Oncogene Proteins c-rel
  • RNA, Small Interfering