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

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Abstract
THE human proto-oncogene myc encodes a nuclear phosphoprotein whose primary biochemical function is still unknown1,2. 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 El A protein and the hormone binding domain of the rat glucocorticoid receptor were shown to activate transcription in a manner characteristic for El A, but in a hormone regulated manner10. We there-fore asked whether the same strategy could be applied to the product of myc.