In vitro "progression" of bovine papillomavirus-transformed cells: loss of contact sensitivity after multiple rounds of selection.

The transformed phenotype of C127 cells harboring bovine papillomavirus shuttle vector pdBPVMMT neo(342-12) was suppressed by direct contact with untransformed C127 cells. By repeated selections of rare foci developing on untransformed cell monolayers, we obtained a cellular clone of BPV transformants which formed foci on the untransformed C127 cells as efficiently as on plastic surface. The BPV genome in the mutant cells showed extensive genetic rearrangements, duplication of upstream regulatory region and deletion of pBR322-derived sequence and its flanking. There was an increase in BPV-transformant in contact with the untransformed C127 cells resulted in a marked reduction of the BPV transcripts, while in the case of the mutant transformant the reduction was much slighter. This indicates that the transcription level of the BPV genome was controlled by a cell-cell contact signal.