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

Abstract

Melanoma progression and resistance to therapy is associated with faulty regulation of signaling 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 up‐regulation 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, in chromosomal stability. Our results highlight a novel tumor‐promoting function of c‐Rel in human melanoma cells through governing cell cycle regulation.

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