Melanoma-associated genes, MXI1, FN1, and NME1, are hypoxia responsive in murine and human melanoma cells.

Hypoxia can influence aggressiveness of melanoma by inducing specific gene expression profiles. In our previous microarray study, we identified more than 430 hypoxia-responsive genes in the B16-F10 murine melanoma cell line in vitro. Of the genes identified, seven genes: galectin 3 (Lgals3), melanoma cell adhesion molecule (Mcam), fibronectin 1 (Fn1), signal transducer and activator of transcription 3 (Stat3), microphthalmia-associated transcription factor (Mitf), max interacting protein 1 (Max1), and non-metastatic cells 1, protein (NM23A) expressed in (Nme1) are known to be associated with melanoma, but have not yet been reported as being regulated by hypoxia in human melanoma cells. In this study, we investigated whether the expression of these genes is modulated by hypoxia in microdissected areas of experimental B16-F10 tumors in vivo, as well as in commercially available human melanoma cell lines (WM35, WM1552C, WM793B, WM278, 1205Lu, and 451Lu) exposed to hypoxic conditions in vitro. Our analysis revealed significant agreement between the in-vitro and in-vivo results showing that all genes except Mitf were hypoxia regulated in the oxygen-deprived tumor regions (P<0.05). In contrast, three genes (NME1, MXI1 and FN1) proved to be hypoxia regulated in both human and mouse melanoma cells (P<0.05). Our results link these genes, for the first time, with hypoxic microenvironment of melanoma and imply that the widely used B16-F10 melanoma experimental tumor model could be a convenient research tool for further investigation of their role in the development and course of this malignancy.