p21(CIP1/WAF1) is a cyclin-dependent kinase inhibitor that directly inhibits the activity of cyclin E/CDK2 and cyclin D/CDK4/6 complexes and thereby functions as a regulator of cell cycle progression. The transcriptional regulation of p21 has been reported to be controlled by a large number of genes. However, the importance of each of these genes upon p21 transcriptional expression in melanoma is not fully explored. Here we have measured p21 mRNA levels in a cell panel consisting of 17 cell melanoma lines with various genetic backgrounds, spanning various stages of the disease. A correlation between p21 expression and p53 status in these cell lines demonstrated low p21 expression in p53 mutant cell lines, such as WM1366, MeWo, SKMEL28, WM45.1, WM983 and WM852 compared to cell lines with wild-type p53. With the use of a number of small molecular inhibitors against the MAPK and cAMP pathways to investigate possible changes in the p21 expression levels, we find that p21 expression levels were more sensitive to regulation by inhibitors in the p53 mutant cell lines compared to cell lines with p53 wild-type. Furthermore, we investigated mRNA expression levels of around 20 genes that previously have been reported to be involved in the regulation of p21 expression, and we find that TBX2 and TBX3 mRNA levels showed the strongest correlation with p21 mRNA levels.

Citation Format: Sigurd L. Bøe, Josef Thingnes, Sima Z. Golmakani, Eivind Hovig. Regulators of p21 transcription in melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4197. doi:10.1158/1538-7445.AM2014-4197

©2014 American Association for Cancer Research.
2014