Reprogramming factors induce proliferation and inhibit apoptosis of melanoma cells by changing the expression of particular genes

Uncontrolled proliferation and defective apoptosis are two major factors responsible for maintaining the malignant properties of melanoma cells. Our previous study demonstrated that induced expression of four reprogramming factors remodeled the phenotype of B16-F10 mouse melanoma cells into melanoma stem cells. The present study was conducted to investigate the effect of the four Yamanaka reprogramming factors, namely Oct4, Sox2, Klf4 and c-Myc (OSKM), on the proliferation and apoptosis of melanoma cells, and to identify the responsible molecular signals. The results identified that expression of the four reprogramming factors was highly induced by doxycycline treatment in the stable melanoma cell clone that was transfected with a plasmid expressing these factors, driven by the Tet-On element. It was further confirmed that induced expression of these factors enhanced the proliferation and suppressed the apoptosis of the melanoma cells. In addition, induced OSKM expression increased cell proliferation, accelerated the progression of the cell cycle, and upregulated the mRNA expression levels of Janus kinase 2 (JAK2) and Cyclin-B1. Induced expression of these factors also decreased the apoptosis, as well as upregulated B-cell lymphoma 2 (BCL-2) and downregulated BCL-2-associated X (BAX) mRNA expression levels. Taken together, the results suggested that upregulated JAK2 and Cyclin-B1 may be responsible for the enhanced proliferation of melanoma cells, and that BCL-2 upregulation and BAX downregulation may account for the suppressed apoptosis of these cells.