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

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

Author information

1
Department of Dermatology, Venereology and Allergology, Georg-August-University, University Medical Center Göttingen, Göttingen, Germany.
2
Department of Dermatology, Friedrich Alexander University, Erlangen, Germany.

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

PMID:
30466153
DOI:
10.1111/exd.13848

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