Cooperation in oncogenesis between BK virus early region gene and the activated human c-Harvey ras oncogene

Rapidly growing, undifferentiated brain tumours were induced in newborn Syrian hamsters by intracerebral inoculation of a recombinant DNA (pBK/c-rasA) carrying the BK virus (BKV) early region gene and the activated human c-Harvey-ras (c-Ha-ras) oncogene. Neither of the two genes inoculated alone nor recombinant DNA of the BKV early region gene and the normal human c-Ha-ras proto-oncogene were tumourigenic. Tumour-derived cell lines propagated in culture were immortalized and had growth characteristics consistent with a fully transformed phenotype. Tumours and tumour cell lines contained pBK/c-rasA sequences integrated into cellular DNA and expressed BKV- and c-Ha-ras-specific transcripts as well as BKV T antigen and c-Ha-ras p21. These findings are discussed in relation to a possible cooperation or synergism between BKV and cellular oncogenes in human neoplasia.