Cellular Transforming Genes in Cancer

Abstract

Genes which regulate growth in normal cells during differentiation function in response to appropriate signals which allow proliferation and maturation to proceed in an orderly manner. In the neoplastic cell, genetic control of proliferation appears to be lost. Non-neoplastic cells may contain a number of genes with potential transforming activity which are normally well regulated and only expressed at a particular phase of cell differentiation. Abnormal expression of these genes may result in neoplastic growth. Experiments by Cooper and co-workers have addressed the question of potential transforming activity of genes from normal cells [1]. In this series of experiments, DNA from normal cells was prepared, sheared to a size range of 0.5–5.0 kilobases, and transfected as a calcium phosphate precipitate into NIH 3T3 cells. Transforming efficiences of high molecular weight DNAs from these cells were approximately 3 × 10^–4 transformants/μg DNA, while transforming efficiencies for sheared DNAs were tenfold greater. Transforming efficiencies of DNAs from foci isolated in primary transfection of sheared DNA when tested in secondary transfection were 100–1000 fold higher (0.1–1.0 foci/μg DNA), comparable to transforming activities of strongly oncogenic viruses [2, 3]. These studies suggest that normal cell genes, when expressed abnormally, can transform at high efficiencies.

This work was supported by CA26825, CA18689, CA28946, CA06721, and an American Cancer Society Faculty Research Award to G.M.C. and by Biomedical Research Support Grants from the National Cancer Institute and the American Cancer Society