Translational control mechanisms in the progression of cutaneous malignant melanoma: the role of eIF2alpha.

Malignant transformation and tumorigenesis include a complex series of cellular and biomecular events which are not yet completely known. Emerging evidence supports the fundamental role of translational control mechanisms in the modulation of cell functions. Cell growth and proliferation depend on protein synthesis that is regulated, in part, by translational initiation factors. These factors transiently increase in normal cells in response to growth factors and are constitutively elevated in transformed cells. In particular, the eIF2 translation factor seems to be involved in the abnormal regulation of protein synthesis that leads to a tumorigenic phenotype. Recent works suggest the translation factor eIF2 to be involved in the pathogenesis and/or tumour progression in some kind of tumours such as bronchioloaveolar carcinoma, non-Hodgkin lymphomas, breast tumour, brain tumour, gastrointestinal carcinomas, melanoma. Moreover other data indicate that the pERK levels could influence the RAS/RAF/MAPK pathway modifying the cell proliferation parameters. In this study we have analysed the phosphorylated eIF2-alpha and ERK levels in different melanoma cell lines derived from metastatic or primary cutaneous melanoma lesions, as well as in a line from the primary skin lesion of a patient with metastatic melanoma. Our results show higher levels of phosphorylated eIF2alpha and ERK in the metastatic cell lines (including the line from the primary lesion in the patient with distant metastases) as compared to the primary melanoma cell lines. In such cell lines, the gene expression of proteins involved in cell cycle regulation (i.e., cyclin D1 and p53) was also examined. The results of our study suggest the relationship between p-eIF2 alpha and tumoral progression in the malignant melanoma. Further analyses could allow to identify phosphorylated eIF2 as a possible prognostic marker.