Modulation of oncogenic potential by alternative gene use in human prostate cancer

Only a small percentage of primary prostate cancers have genetic changes. I n contrast, nearly 90% of clinically significant human prostate cancers see ms to express high levels of the nuclear phosphoprotein pp32 by in situ hyb ridization. Because pp32 inhibits oncogene-mediated transformation, we inve stigated its paradoxical expression in cancer by comparing the sequence and function of pp32 species from paired benign prostate tissue and adjacent p rostatic carcinoma from three patients. Here we demonstrate that pp32 is ex pressed in benign prostatic tissue, but pp32r1 and pp32r2, closely-related genes located on different chromosomes, are expressed in prostate cancer. A lthough pp32 is a tumor suppressor, pp32r1 and pp32r2 are tumorigenic. Alte rnative use of the pp32, pp32r1 and pp32r2 genes may modulate the oncogenic potential of human prostate cancer.