Characterization of Bovine Papillomavirus Type 1-transformed Clones which Show Distinct Transformed Phenotypes

Abstract

SUMMARYSeventeen independent cell clones were isolated from C127 cells transformed by bovine papillomavirus type 1 (BPV-1). Transformants showed differing degrees of expression of the transformed phenotype as monitored by saturation density, doubling time, growth in medium with a low serum concentration and colony-forming efficiency in soft agar. The degree of expression of the transformed phenotype did not correlate with either the BPV-1 copy number or levels of BPV-l-specific RNA in the transformed cell clones. A characteristic transformed cell clone, Tlc, showed the lowest degree of expression of the transformed phenotype but contained the highest copy number ofBPV-1 DNA and the highest level of BPV-l-specific mRNA. When we analysed different transformants by two-dimensional gel electrophoresis, we found that a set of six proteins changed quantitatively. Changes in the expression of these proteins were most consistent in clones expressing the greatest number of parameters of transformation, e.g. clone T4a. These data indicate that changes in the expression of cellular genes may correlate with the degree of expression of the transformed phenotype.

Bovine papillomavirus type 1-transformed primary mouse fibroblasts show no correlation between tumorigenicity and viral gene expression, but c-myc gene expression is elevated in tumorigenic cell lines

“…Similarly, Heilman et al (1982) did not find any correlation between tumorigenicity of transformed hamster cells and viral transcription. Our results also agree with Tada et al (1989), who demonstrated that in transformed C127 cells there was no correlation between the in vitro parameters of transformation and viral transcription. The authors attributed the degree of expression of the transformed phenotype to changes in the expression of cellular genes.…”

Bovine papillomavirus E2 repressor mutant displays a high-copy-number phenotype and enhanced transforming activity

“…This conclusion was previously suggested by the behavior of BPV-1-transformed hamster cells and C127 cells harboring a low-copy-number BPV-1 mutant (4,39). However, a recent study of BPV-transformed C127 cell clones failed to reveal such a correlation (37). In C127 cells acutely transformed by the BPV-1 E5 protein, there is a clear correlation between the dose of the viral E5 gene and both the extent of morphologic transformation and the ability of the cells to escape growth arrest (33).…”

E5 oncoprotein retained in the endoplasmic reticulum/cis Golgi still induces PDGF receptor autophosphorylation but does not transform cells.

“…The major in vitro transforming protein in BPV-1 is E5 which, at 44 amino acids in length, is the smallest known viral oncoprotein. When E5 is expressed in immortalized murine cells, they become morphologically transformed, proliferate in an anchorage-independent manner and form tumors in nude mice Tada et al, 1989). Structurally,E5 can be divided into two domains.…”