SIMULTANEOUS SUPPRESSION OF PROGRESSION MARKER GENES IN THE HIGHLY MALIGNANT HUMAN-MELANOMA CELL-LINE BLM AFTER TRANSFECTION WITH THE ADENOVIRUS-5 E1A GENE

The highly metastatic human melanoma cell line BLM was transfected wit h the EIA or EIA+EIB regions of adenovirus 5 (Ad5). A series of progre ssion markers, correlated with the malignant phenotype of parental BLM (including calcyclin, thymosin beta 10, plasminogen activator inhibit ors types 1 and 2, urokinase type and tissue type plasminogen activato rs, vimentin, tissue type transglutaminase, and interleukin-6), was co llectively repressed in the transfectants, whereas several control gen es were not affected or even induced. The apparently coordinate repres sion of a set of markers by the same regulator gene, Ad5 EIA in this c ase, suggests the existence of one pathway under the control of a main switch and predicts that one or more as yet unidentified cellular mas ter genes normally exert this function. A reduced oncogenic ity was ob served after subcutaneous inoculation of the EIA transfectants into nu de mice and provides additional evidence in support of a tumor suppres sor function of Ad5 EIA. (C) 1996 Academic Press, Inc.