Chimaeras of myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells.

The human proto-oncogene myc encodes a nuclear phosphoprotein whose primary biochemical function is still unknown. To facilitate further study of that function, we have created conditional alleles of myc by fusing the hormone-binding domain of the human oestrogen receptor gene to the 5' or the 3' end of human myc. The two chimaeric genes, designated mycer and ermyc, encode proteins that bind oestrogen with high affinity. Expression of one of the genes, mycer, transforms a rat fibroblast cell line in a tightly oestrogen-dependent manner. Transformation is dependent on the presence of a functional myc gene in the chimaera and is reversible upon removal of the hormone. The chimaeric genes will be useful tools to study the mechanisms by which Myc affects cellular phenotype. Recently, chimaeras between the adenovirus E1A protein and the hormone binding domain of the rat glucocorticoid receptor were shown to activate transcription in a manner characteristic for E1A, but in a hormone regulated manner. We therefore asked whether the same strategy could be applied to the product of myc.