Co‐operation in cell transformation between BK virus and the human C‐harvey‐ras oncogene

Abstract

Early-passage hamster embryo cells were transformed by recombinant DNA molecules containing BK virus (BKV) early-region gene and either the activated c-Ha-ras oncogene (pBK/c-rasA) or the normal c-Ha-ras proto-oncogene (pBK/c-rasN). The recombinant DNAs had a greater transforming ability and converted hamster cells to a more malignant phenotype than the single genes transfected separately. pBK/c-rasA was significantly more powerful than pBK/c-rasN in conferring to cells all the characteristics of transformation. Transfected DNA sequences were integrated mostly as single insertions into cellular DNA. Specific c-Ha-ras and BKV transcripts as well as c-Ha-ras p21 and BKV T antigen were detected in transformed cells. Although stimulation of c-Ha-ras expression by BKV enhancers cannot be excluded in recombinants, super-transfection and co-transfection experiments in hamster embryo cells and pre-neoplastic cell lines showed that BKV early-region and c-Ha-ras co-operate in transformation by contributing separate and independent functions.

Characterization of BK virus variants rescued from human tumours and tumour cell lines

“…Fig the entire BKV early region cooperates with activated c-ras in the induction of the transformed phenotype (Pagnani et al, 1988). These experiments show that a specific BKV variant is associated with human brain tumours, osteosarcomas and African KS.…”

“…To test the enhancer activity in transformation, BKV-IR or BKV-WT HindlII fragment C were placed upstream of the activated human c-ras oncogene and the recombinants were transfected into Rat-1 cells. As shown in Table 4, pBode-IR/c-rasA produces a significantly higher number of transformed foci than pBode-WT/c-rasA and pBR/c-rasA which does not contain BKV sequences (Pagnani et aL, 1988 41-2 1-5 x 10 -6 0 * Plating efficiency was calculated as the ratio between the number of colonies and the number of cells plated (2 x 102/10 cm Petri dish) under non-selective conditions. t The mutation frequency (Mr) was calculated by the formula Mf = M/CE, where M is the number of mutants obtained, C is the total number of cells plated (1.5 x 107) and E is the plating efficiency.…”

The human polyomaviruses

“…In general, the degree of transforming capacity displayed by JCV in experimental animals and cultured cells is greater than that seen with BKV. The latter virus transforms cell lines with limited success and often requires the auxiliary function of other more potent oncogenes [152]. Similarly, in animal models the transformation efficiency of BKV is contingent upon the route of inoculation and the strain of the virus [151].…”

BK polyomavirus association with colorectal cancer development

“…Several research groups have drawn attention to the high tumorigenic potential of BKV. For instance, it is able to transform rodent cells into malignant neoplasm, and eternalize human cells alone or in combination with other oncogene families including myc and ras (Portolani et al, 1975;Grossi et al, 1982;Pagnani et al, 1988;Kenan et al, 2015). BKV inoculation into animal models causes the development of various neoplasms, including glioma, neuroblastoma, ependymoma, osteosarcoma, liposarcoma, and fibrosarcoma, among others (Tognon et al, 2003).…”