Reversible Conversion of Cells Between Cancerous and Normal States

A comparison of the chromosomal organisation of various genes in clusters has shown that when two genes lie on the same DNA strand and have an intergenic distance shorter than a defined length, the transcriptional activities of one or both genes are, in most cases, absent or greatly reduced. Based on this observation, we used cell lines (derived from NIH/3T3 cells) in which human mutated c-H-ras was closely linked to another gene, e.g. E. coli xanthine-guanine phosphoribosyltransferase (gpt) gene with the SV40 promoter, on the same DNA strand of the chromosome to examine the possibility that oncogene expression suffers interference from a cis-acting gene-to-gene interaction and as a result, cell transformation and the cancerous nature of cells can be altered. We present evidence that the cancerous nature of cells is readily converted to the“normal”state by the enforced expression of the neighbouring gpt gene and vice versa.