In this research, gene transfer methods will be used to relate the structural features of translocated c-myc genes to their tissue-specific transcriptional activation. Protein-DNA interactions on regions of DNA implicated in gene activation will be sought. The consequences for cells of activated c-myc expression also will be studied. Will nonactivated c-myc genes be switched off in such cells because of an autoregulation mechanism? Subtracted cDNA libraries will be constructed using tumor cells that contain translocated c-myc and nontumorigenic cells that are proposed to be their premalignant precursors. This approach may prove more widely applicable to other related cells in tumorigenesis. Finally, I shall employ biological assays that I have developed for c-myc, in order to screen for activated c-myc (and c-myc-like) genes from other tumors, and, in addition, to delineate regions of c-myc protein responsible for its biological effects. (X)
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