The Search for Oncogenes in Breast Cancer

Abstract

The concept of oncogenes has evolved impressively with the demonstration of the conferral onto cultured cells of a dominant transformed phenotype by tumor cell DNA mediated gene transfer (1–3). Genomic DNA transfection and the stable acquisition of transfected DNA by acceptor cells allows the distribution of tumor cell DNA into phenotypically normal cells. The rare transformation of a normal cell by the transfected DNA, ie., at best 1 in 10³ acceptor cells is able to stably acquire DNA and 1 in 10³ stably transfected cells acquires a single specific gene, is accomplished by the uptake of oncogenes (4). This experimental protocol has led to the identification, molecular cloning and characterization of several cellular oncogenes and to the description of their mode of activation (5). The detection of oncogenes in primary tumor tissue, however, has not generally been successful (6)NIH/3T3 cells were originally chosen as acceptor cells because they can be efficiently transfected and it is possible to morphologically distinguish transformed from non-transformed cells. But there are certain limitations to the oncogene detection assay based on tumor DNA transfer into NIH/3T3 cells and focus formation of dense cells on the background of unaffected cells, a) Differentiation specific genes have been found to be restricted in their control of expression.