Oncogenes seem to transform cells through a common pathway(s), which perhaps involves cellular growth regulatory systems including growth control coupled to cell-cell contacts, growth factor production and cell cycle controls. In order to elucidate this pathway, we have been attempting to molecularly clone cellular genes having transforming potential by utilizing the cDNA expression cloning system we developed. Transfection of NIH3T3 cels with a SV40-transformed human fibroblast cDNA library constructed in a mammalian expression vector have yielded 30 independent morphologically transformed colonies. In order to clone integrated transforming cDNAs, lambda genomic libraries were constructed with total genomic DNAs of each transformant and are currently being screened by plaque hybridization with the vector sequence as a probe. Overlapping lambda clones have been so far recovered from two primary transformants, and found to be able to transform cells. The lambda clones can induce foci but little if any morphological changes. These clones do not have any significant homology to major known oncogenes. Characterization of these clones is currently in progress. The clone reported last year was found to contain a part of the SV40 VP3 capsid protein gene. Preliminary experiments indicate that the intact VP3 gene may have weak transforming activity.
