Cellular genes possibly involved in the transformation process of the human melanoma cell line XP44 RO (Mel)

P44 Ro (Mel) is a human malignant melanoma cell line derived from a testicular metastasis in a DNA repair deficient, xeroderma pigmentosum patient. This line harbors a N-ras gene mutated in codon 61. To investigate other cellular genes possibly contributing to the expression of its transformed phenotype, four XP44 revertant cell lines were isolated by different selection procedures and the association of the level of expression of various oncogenes (including N-ras) and tumor suppressor genes with the selection for the revertant phenotype was determined. The revertants exhibited a significant but variable degree of phenotypic reversion, according to the selective pressure to which they were submitted, and a phenotypic stability dependent on their constant maintenance in selective medium. Back-revertant lines were isolated by culturing revertant lines in control medium for several weeks. The comparison between parental, revertant and back-revertant cells has revealed that, beyond the mutation in codon 61 of N-ras, two groups of genes appear to be also implicated in the transformation process of XP44 RO (Mel) cells: one group, comprising pim A, trk, Rb and p53, whose expression is independent of the cell selection conditions; the other group, comprising Ha-ras, N-ras, neu 1, fos and met H, whose expression is more or less dependent upon such conditions. The myc gene is apparently not involved in this phenomenon. These results, besides strengthening the concept that carcinogenesis is a multigenic process, suggest that diverse mechanisms can lead to the transformed phenotype, but that these mechanisms might have some pathway(s) in common.