INFLUENCE OF A HAMSTER TUMOR-SUPPRESSOR GENE ON TRANSFORMATION BY VIRAL AND CELLULAR ONCOGENES

To determine if the tumor suppressor gene active in BHK hamster cells acts to maintain the normal phenotype by influencing oncogene transfor mation, careful, quantitative transfections with a variety of oncogene s were performed on four closely related BHK subclones. Two of the clo nes had an active suppressor gene (sup+ clones) and two of them had lo st the suppressor (sup- clones) yet remained anchorage dependent. Both sup+ and sup- clones could be transformed to anchorage independence b y ras, src, mos, neu, polyoma mT and SV40 suggesting that neither the presence nor the absence of the suppressor gene in BHK limits the tran sforming ability of these common oncogenes. All lines were resistant t o transformation by N-myc, EIA and c-sis, oncogenes that may perform r edundant functions in the immortal, fast growing BHK cell. SV40 small t antigen which has previously been considered unable to transform cul tured cells by itself, was nevertheless able to transform sup+ BHK lin es to anchorage independence in the absence of the viral large T antig en. Clones of sup- cells expressing high levels of small t antigen pro tein could be isolated, but they remained anchorage dependent and in t umorigenicity assays retained the long latent period characteristic of normal BHK cells. Such lines should enable the identification of cell ular targets vital to the transforming function of SV40 small t.