CELLULAR GENES POSSIBLY INVOLVED IN THE TRANSFORMATION PROCESS OF THEHUMAN-MELANOMA CELL-LINE XP(44)RO (MEL)

P44 Ro (Mel) is a human malignant melanoma cell line derived from a te sticular metastasis in a DNA repair deficient, xeroderma pigmentosum p atient. This line harbors a N-ras gene mutated in codon 61. To investi gate other cellular genes possibly contributing to the expression of i ts transformed phenotype, foul 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 suppresso r genes with the selection for the revertant phenotype was determined The revertants exhibited a significant bur variable degree of phenotyp ic reversion, according to the selective pressure to which they were s ubmitted, and a phenotypic stability dependent on their constant maint enance in selective medium Back-revertant lines were isolated by cultu ring revertant lines in control medium for several weeks. The comparis on between parental, revertant and back-revertant cells has revealed t hat, beyond the mutation in codon 61 of N-ras, two groups of genes app ear to be also implicated in the transformation process of XP(44) RO ( Mel) cells: one group, comprising pim A, trk, Rb and p53, whose expres sion is independent of the cell selection conditions; the other group, comprising Ha-ras, N-ras, neu I, fos and met H, whose expression is m ore 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 th ese mechanisms might have some pathway(s) in common.